ascorbic-acid and Inflammation

COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2.. We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022.. Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation.. There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Topics: Ascorbic Acid; COVID-19; Critical Illness; Humans; Inflammation; Micronutrients; Nitrogen; Nutritional Requirements; SARS-CoV-2; Trace Elements; Vitamin A; Vitamin B Complex

Hemodialysis (HD) is the most common method of renal replacement therapy. Besides toxins, it eliminates nutrients from the circulation, such as ascorbic acid (AA). HD-patients present AA deficiency more often than representatives of the general population, also due to dietary restrictions. This condition aggravates oxidative stress and inflammation related to uremia and extracorporeal circulation and increases cardiovascular risk followed by mortality. Supplementation of AA seems to be a promising approach in the treatment of hemodialysis patients. Many successful interventions restored plasma AA concentration in HD patients by enteral or intravenous supplementation, concomitantly inhibiting oxidative stress and inflammation. A significant number of studies reported opposite, serious pro-oxidant effects of AA. In this narrative review, we present studies, commenting on their limitations; on AA plasma or serum concentration and the influence of its supplementation on protein and lipid peroxidation, DNA damage, reactive oxygen species generation, paraoxonase activity, advanced glycation endproducts, and C-reactive protein (CRP) concentration. Moreover, in terms of safety, the possible development of oxalosis in HD patients regarding the intravenous or enteral route of AA administration is discussed. Unequivocal clinical results of recent studies on hemodialysis patients are displayed.

Topics: Ascorbic Acid; Humans; Inflammation; Oxidative Stress; Renal Dialysis; Vitamins

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Compared with adults, children with SARS-CoV-2 infection may have fewer and less severe symptoms. Gastrointestinal symptoms are commonly reported in children, sometimes as the only manifestation of the disease, and most often manifest as anorexia, diarrhea, nausea and vomiting, or abdominal pain. Although most children have asymptomatic or mild disease, 10 % of those infected may experience serious or critical disease, or even death. Multisystem inflammatory syndrome is a rare but serious condition recently reported in children with COVID-19. Studies indicate that children with obesity are at higher risk of developing severe COVID-19, and inflammation associated with obesity could be one of the factors that worsens COVID-19 symptoms due to an increased inflammatory response involving molecules such as interleukin 6, tumor necrosis factor alpha, and monocyte chemoattractant protein. On the other hand, evidence has been reported of a higher protein expression of ACE2 in the visceral adipose tissue of obese and malnourished humans, and this could be associated with complications and severity of COVID-19. Therefore, regulation of the intake of macronutrients or micronutrients could be used as a strategy to reduce the consequences of COVID-19. Diet in general and bioactive compounds could play an important role in the prevention of the inflammatory cascade. The micronutrients with the most evidence suggesting a role in immune support are vitamins C and D, zinc, and polyphenols.. La enfermedad por coronavirus 2019 (COVID-19) está causada por el virus “síndrome respiratorio agudo severo-coronavirus 2” (SARS-CoV-2). En comparación con los adultos, los niños con infección por SARS-CoV-2 pueden tener menos síntomas y estos pueden ser menos graves. Los síntomas gastrointestinales se informan comúnmente en los niños, a veces como única manifestación de la enfermedad. Los más comunes son anorexia, diarrea, náuseas y vómitos, y dolor abdominal. Aunque la mayoría de los niños tienen un cuadro leve o asintomático, el 10 % de los infectados pueden experimentar un cuadro grave o crítico, e incluso la muerte. El síndrome inflamatorio multisistémico es una afección poco común, pero grave, que se documentó recientemente en niños con COVID-19. Los estudios indican que los niños con obesidad tienen mayor riesgo de desarrollar COVID-19 grave, y la inflamación asociada con la obesidad podría ser uno de los factores que empeoran los síntomas de la COVID-19 debido a una respuesta inflamatoria aumentada en donde se ven involucradas moléculas como la interleucina 6, el factor de necrosis tumoral alfa y la proteína quimioatrayente de monocitos. Por otro lado, se ha encontrado evidencia de una mayor expresión proteica de ACE2 en el tejido adiposo visceral de los seres humanos obesos y desnutridos, y esto podría estar asociado a las complicaciones y la severidad de la COVID-19. Por tanto, la regulación de la ingesta de macronutrientes o micronutrientes podría utilizarse como estrategia para reducir las consecuencias de la enfermedad. La dieta en general y los compuestos bioactivos podrían desempeñar un papel importante en la prevención de la cascada inflamatoria. Los micronutrientes con mayor evidencia indicativa de que desempeñan un papel en el apoyo inmunológico son las vitaminas C y D, el zinc y los polifenoles.

Topics: Abdominal Pain; Angiotensin-Converting Enzyme 2; Anorexia; Ascorbic Acid; Child; COVID-19; Diarrhea; Female; Gastrointestinal Diseases; Humans; Inflammation; Male; Nausea; Overweight; Oxidative Stress; Pediatric Obesity; Polyphenols; Systemic Inflammatory Response Syndrome; Thinness; Vitamin D; Vitamins; Vomiting; Zinc

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.

Topics: Ascorbic Acid; C-Reactive Protein; COVID-19; COVID-19 Drug Treatment; Dietary Supplements; Humans; Immune System; Inflammation; Melatonin; Meta-Analysis as Topic; SARS-CoV-2; Trace Elements; Vitamin D; Vitamins; Zinc

The immune system provides defence to the host against pathogenic organisms. A weak immune system increases susceptibility to infections and allows infections to become more severe. One component of the immune response is inflammation. Where inflammation is excessive or uncontrolled it can damage host tissues and cause pathology. Limitation of oxidative stress is one means of controlling inflammation. Citrus fruit juices are a particularly good source of vitamin C and folate, which both have roles in sustaining the integrity of immunological barriers and in supporting the function of many types of immune cell including phagocytes, natural killer cells, T-cells and B-cells. Vitamin C is an antioxidant and reduces aspects of the inflammatory response. Important bioactive polyphenols in citrus fruit juices include hesperidin, narirutin and naringin. Hesperidin is a glycoside of hesperetin while narirutin and naringin are glycosides of naringenin. Hesperidin, hesperetin, naringenin, naringin and narirutin have all been found to have anti-inflammatory effects in model systems, and human trials of hesperidin report reductions in inflammatory markers. In humans, orange juice was shown to limit the post-prandial inflammation induced by a high fat-high carbohydrate meal. Consuming orange juice daily for a period of weeks has been reported to reduce markers of inflammation, including C-reactive protein, as confirmed through a recent meta-analysis. A newly emerging topic is whether polyphenols from orange juice have direct anti-viral effects. In summary, micronutrients and other bioactives present in citrus fruit juices have established roles in controlling oxidative stress and inflammation and in supporting innate and acquired immune responses. Trials in humans demonstrate that orange juice reduces inflammation; its effects on innate and acquired immunity require further exploration in well-designed trials in appropriate population sub-groups such as older people.

Topics: Antioxidants; Ascorbic Acid; Biological Availability; Biomarkers; Citrus; Citrus sinensis; Folic Acid; Fruit and Vegetable Juices; Glycosides; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunocompetence; Inflammation; Micronutrients; Models, Immunological; Molecular Structure; Oxidative Stress; Pathogen-Associated Molecular Pattern Molecules; Phytotherapy; Polyphenols

Vitamin C (ascorbic acid) seems to attenuate the overproduction of reactive species during and after exercises. Yet, no meta-analysis has summarized the magnitude of this effect. The objective of this study was to systematically review the effects of vitamin C supplementation on oxidative stress, inflammatory markers, damage, soreness, and the musculoskeletal functionality after a single bout of exercise.. Major electronic databases were searched, from inception to September 2019, for placebo-controlled randomized clinical trials (RCTs) that evaluated the effects of vitamin C supplementation on oxidative stress parameters, inflammation markers, muscle damage, muscle soreness, and muscle functionality after a single bout of exercise in healthy volunteers. Random-effects modelling was used to compare mean changes from pre- to postexercise in participants that were supplemented with vitamin C versus placebo. Data were reported as standard mean difference (SMD) and 95% confidence interval (CI).. A total of 18 RCTs, accounting for 313 participants (62% males, median age = 24 years) were included. Vitamin C supplementation reduced lipid peroxidation immediately (SMD = - 0.488; 95% CI = - 0.888 to - 0.088), 1 h (SMD = - 0.521; 95% CI = - 0.911 to - 0.131) and between 1 and 2 h (SMD = - 0.449; 95% CI = - 0.772 to - 0.126) following exercise. Exercise induced interleukin-6 (IL-6) response was attenuated 2 h (SMD = - 0.764; 95% CI = - 1.279 to - 0.248) and between 1 and 2 h (SMD = - 0.447; 95% CI = - 0.828 to - 0.065) after exercise. No effects of vitamin C supplementation were found on creatine kinase (CK), C-reactive protein (CRP), cortisol levels, muscle soreness, and muscle strength.. Vitamin C supplementation attenuates the oxidative stress (lipid peroxidation) and inflammatory response (IL-6) to a single bout of exercise.. PROSPERO (CRD42018094222).

Topics: Adult; Ascorbic Acid; Dietary Supplements; Exercise; Female; Humans; Inflammation; Male; Muscle Strength; Muscle, Skeletal; Myalgia; Oxidative Stress; Randomized Controlled Trials as Topic; Young Adult

To assess whether a standardized dietary supplementation can help to decrease postoperative muscle atrophy and/or improve rehabilitation outcomes in patients who underwent anterior cruciate ligament reconstruction (ACLR).. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). MEDLINE, Scopus, and Cochrane Library databases were searched, and articles that examined protein or amino acid, vitamin, or any other type of supplementation in ACLR were reviewed. Two independent reviewers conducted the search using pertinent Boolean operations.. A total of 1818 articles were found after our database search. Ten studies fulfilled our inclusion criteria and only assessed patients undergoing ACLR. Four studies assessed protein-based supplementation. One study assessed creatine as a supplement. Four studies assessed vitamin-based supplementation. One study assessed testosterone supplementation. Protein and amino acid supplementation showed potential benefits; multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, graft maturation, muscular hypertrophic response, and peak dynamic muscle strength. When we examined creatine, vitamin, or hormone-based protocols, none demonstrated results, suggesting these factors may attenuate muscle atrophy after surgery. Vitamin C and E demonstrated potentially increased local inflammation in skeletal muscle, which runs contrary to the belief that antioxidant vitamin-based supplementation may decrease the inflammatory response that plays a role in the post injury/operative period.. Protein-based supplementation may play a role in mitigating muscle atrophy associated with ACLR, as multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, thigh hypertrophic response, and peak dynamic muscle strength. However, based on current literature, it is not possible to recommend a specific protein-based supplementation protocol at this time for patients undergoing ACLR. Limited evidence suggests no benefit for creatine, vitamin, or hormone-based protocols.. II, a systematic review of level I-II studies.

Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Ascorbic Acid; Creatine; Dietary Supplements; Humans; Inflammation; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Vitamin E

Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Inflammation; Metabolic Syndrome; Oxidative Stress

This review discusses the chemical mechanisms of ascorbate-dependent reduction and solubilization of ferritin's ferric iron core and subsequent release of ferrous iron. The process is accelerated by low concentrations of Fe(II) that increase ferritin's intrinsic ascorbate oxidase activity, hence increasing the rate of ascorbate radical formation. These increased rates of ascorbate oxidation provide reducing equivalents (electrons) to ferritin's core and speed the core reduction rates with subsequent solubilization and release of Fe(II). Ascorbate-dependent solubilization of ferritin's iron core has consequences relating to the interpretation of

Topics: Ascorbate Oxidase; Ascorbic Acid; Ferritins; Humans; Inflammation; Iron; Iron Radioisotopes; Oxidation-Reduction; Reactive Oxygen Species; Transferrin

Workers involved in mining activities are exposed to crystalline silica, which leads to constant pulmonary inflammatory reactions and severe oxidative damage, resulting in silicosis. In this work, we aimed to evaluate inflammatory and oxidative stress parameters as potential early biomarkers of effect to assess crystalline silica toxicity in workers who had occupational exposure during mining. We enrolled 38 workers exposed to crystalline silica (WECS), 24 individuals with silicosis (IWS), and 30 occupationally unexposed workers (OUW), a total of 92 participants. The WECS were divided into 2 groups, according to the time of exposure: 19 workers with 1-15 years of occupational exposure (WECS I) and 19 workers with >16 years of occupational exposure (WECS II). The inflammatory parameters assessed were L-selectin, β-2 integrin, and intercellular adhesion molecule-1 (ICAM-1) surface protein expression in lymphocytes and monocytes, complement C3 and C4, high sensitivity C-reactive protein (hsCRP), and adenosine deaminase (ADA) in serum. Plasma levels of malondialdehyde (MDA) and serum levels of vitamin C were determined as biomarkers of oxidative stress. Biochemical and hematological parameters were also investigated. L-selectin surface protein expression was significantly decreased in the WECS II group (p < 0.05), indicating the importance of this immune system component as a potential marker of crystalline-silica-induced toxicity. The MDA levels were significantly increased in the WECS I, WECS II, and IWS groups compared to the OUW group (p < 0.05). Vitamin C levels were decreased, while C3, hsCRP, ADA, and aspartate aminotransferase (AST) levels were increased in the IWS group compared to the OUW group (p < 0.05). Glucose and urea levels were significantly higher in the WECS I, II, and IWS groups compared to the OUW group (p < 0.05). Negative partial association was found between L-selectin and time of exposure (p < 0.001), supporting the relevance of this biomarker evaluation in long-term exposure to crystalline silica. Significant associations were also observed among inflammatory and oxidative stress biomarkers. Therefore, our results demonstrated the relevance of L-selectin as a potential peripheral biomarker for monitoring crystalline silica-induced toxicity in miners after chronic exposure, before silicosis has developed. However, more studies are necessary for better understanding of the use L-selectin as an early biomarker in exposed workers.

Topics: Ascorbic Acid; Biomarkers; Humans; Inflammation; Malondialdehyde; Oxidative Stress; Silicosis

Vitamin C (ascorbate) is maintained at high levels in most immune cells and can affect many aspects of the immune response. Intracellular levels generally respond to variations in plasma ascorbate availability, and a combination of inadequate intake and increased turnover during severe stress can result in low plasma ascorbate status. Intracellular ascorbate supports essential functions and, in particular, acts as an enzyme cofactor for Fe- or Cu-containing oxygenases. Newly discovered enzymes in this family regulate cell metabolism and epigenetics, and dysregulation of their activity can affect cell phenotype, growth and survival pathways, and stem cell phenotype. This brief overview details some of the recent advances in our understanding of how ascorbate availability can affect the hydroxylases controlling the hypoxic response and the DNA and histone demethylases. These processes play important roles in the regulation of the immune system, altering cell survival pathways, metabolism and functions.

Topics: Animals; Ascorbic Acid; Cell Hypoxia; Copper; Dendritic Cells; Epigenesis, Genetic; Histone Demethylases; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immune System; Inflammation; Iron; Killer Cells, Natural; Macrophages; Mice; Monocytes; Neoplasms; Neutrophils; Phenotype; Signal Transduction; Stem Cells; T-Lymphocytes

The present meta-analysis was designed to assess the effects of vitamin C supplementation on serum C-reactive Protein (CRP) levels.. We conducted a comprehensive systematic search of the literature in Scopus, PubMed and Google Scholar until May 2018. The pooled Weighted Mean Difference (WMD) and its 95% Confidence Interval (CI) in baseline and at the end of the trial were calculated to assess the net change in serum CRP by using random-effects model. The heterogeneity was assessed by I2 test. Combined and stratified analyses were used in the metaanalysis.. From 306 articles found and screened in our initial search, 12 studies were included with 446 participants in supplementation groups and 447 in control groups. The pooled effect size analysis showed a significant reducing effect of vitamin C supplementation on circulating CRP level (-0.23 mg/L, 95% CI, -0.44, -0.03, p=0.02), with a significant heterogeneity effect across the studies involved. Subgroup analyses showed that vitamin C supplementation significantly lowered CRP among trials. The most significant effect was found 1) on hs- CRP as the representative inflammatory marker (-0.43 mg/L, 95% CI -0.76, -0.1) 2) in subjects with a baseline CRP≥3 (-1.48 mg/L, 95% CI -2.84, -0.11) 3) in subjects under <60 years old of age (-0.23 mg/L, 95% CI -0.44,- 0.01) 4) or using intravenous administration of vitamin C (-0.89 mg/L, 95% CI -1.49,-0.3).. The present meta-analysis shows that vitamin C supplementation reduces serum CRP level, particularly in younger subjects, with higher CRP baseline level, at a lower dosage and intravenous administration.

Topics: Ascorbic Acid; Biomarkers; C-Reactive Protein; Dietary Supplements; Humans; Inflammation; Randomized Controlled Trials as Topic

Obesity means the accumulation of excessive fat that may interfere with the maintenance of optimal state of health. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type-2 diabetes mellitus, and dyslipidemia, but there are evidences for other mediators such as chronic inflammation, oxidative stress, and thrombosis. The decreased levels of antioxidants factors and nitric oxide predispose to further cardiovascular adverse events. To reduce the risks, antioxidants can help by neutralizing the free radicals and protecting from damage by donating electrons. Having the capacity, vitamin C protects from oxidative stress, prevention of non-enzymatic glycosylation of proteins, and enhances arterial dilation through its effect on nitric oxide release. It also decreases lipid peroxidation, and alleviates inflammation. The anti-inflammatory property of vitamin C could be attributed to ability to modulate the NF-

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Humans; Inflammation; Obesity; Oxidative Stress

Investigations to discover new biomarkers of nutrition highlighted the fact that inflammation and infection were cross-cutting issues complicating interpretation of status. Collaborative groups of nutritionists, immunologists, clinicians and statisticians were set up to investigate the issues, and some are now reporting their findings.. Recent work on the vitamins A, D, E and C and the elements iron, zinc and selenium are reported in this review. In clinical settings, experts emphasize the unreliability of nutritional biomarkers to reflect status, but some advocate the use of albumin to assist interpretation. In apparently healthy people with subclinical inflammation, one method to correct data on vitamin A and iron stores using C-reactive protein and alpha-1-acid glycoprotein is available, and two studies report on its use; others methods are currently being investigated.. Biomarkers of most micronutrients are the plasma concentrations of the respective vitamins or minerals and, irrespective of nutritional status, many are reduced by inflammation; the main exception is ferritin which is increased. Different methods are being investigated to better interpret nutritional data in the presence of infection or inflammation, and nutritionists who work with apparently healthy people need to be aware of subclinical inflammation to avoid exaggerating or underreporting nutritional results.

Topics: Ascorbic Acid; Biomarkers; C-Reactive Protein; Dietary Supplements; Ferritins; Humans; Inflammation; Iron; Micronutrients; Nutritional Status; Selenium; Serum Albumin; Vitamin A; Vitamin D; Vitamin E; Zinc

Lipoic acid (LA) is an antioxidant able to produce its effects in aqueous or lipophilic environments. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. It presents a highly negative reduction potential, increases the expression of antioxidant enzymes and participates in the recycling of vitamins C and E. Due to these properties, LA is called the "universal antioxidant". LA is also involved with anti-inflammatory action, independently of its antioxidant activity. This review was carried out, aiming to identify, analyze, and rationalize the various clinical, physiopathological and/or physiological situations in which LA, through oral supplementation, was tested on human and animal (rats and mice) models. LA was mainly tested in cardiovascular diseases (CVD), obesity, pain, inflammatory diseases and aging. LA uses in CVD and obesity, in humans, are controversial. On the other hand, beneficial effects on inflammation and pain were observed. LA supplementation in animal models may prolong life, has neuroprotective effects and presents positive effects against cancer. Differences observed in human and animal models can be due, in part, to different treatments (LA combined with other antioxidants, different doses) and to the variety of biomarkers investigated in animal experiments. These results suggest the need for further clinical trials to guide health professionals regarding the safety of prescription of this supplement.

Topics: Aging; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Disease Models, Animal; Humans; Inflammation; Oxidative Stress; Pain; Reactive Oxygen Species; Thioctic Acid; Vitamin E

The concept of mild chronic vascular inflammation as part of the pathophysiology of cardiovascular disease, most importantly hypertension and atherosclerosis, has been well accepted. Indeed there are links between vascular inflammation, endothelial dysfunction and oxidative stress. However, there are still gaps in our understanding regarding this matter that might be the cause behind disappointing results of antioxidant therapy for cardiovascular risk factors in large-scale long-term randomised controlled trials. Apart from the limitations of our knowledge, limitations in methodology and assessment of the body's endogenous and exogenous oxidant-antioxidant status are a serious handicap. The pleiotropic effects of antioxidant and anti-inflammation that are shown by some well-established antihypertensive agents and statins partly support the idea of using antioxidants in vascular diseases as still relevant. This review aims to provide an overview of the links between oxidative stress, vascular inflammation, endothelial dysfunction and cardiovascular risk factors, importantly focusing on blood pressure regulation and atherosclerosis. In view of the potential benefits of antioxidants, this review will also examine the proposed role of vitamin C, vitamin E and polyphenols in cardiovascular diseases as well as the success or failure of antioxidant therapy for cardiovascular diseases in clinical trials.

Topics: Animals; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Endothelium, Vascular; Humans; Hypertension; Inflammation; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Vitamin E

Randomised controlled trials (RCT) testing the effects of antioxidant supplements on endothelial function (EF) have reported conflicting results. We aimed to investigate the effects of supplementation with antioxidant vitamins C and E on EF and to explore factors that may provide explanations for the inconsistent results. We searched four databases (MEDLINE, Embase, Cochrane Library and Scopus) from inception until May 2014 for RCT involving adult participants aged ≥18 years who were supplemented with vitamins C and E alone or in combination for more than 2 weeks and reporting changes in EF measured using flow mediated dilation or forearm blood flow. Data were pooled as standardised mean difference (SMD) and analysed using a random-effects model. Significant improvements in EF were observed in trials supplementing with vitamin C alone (500-2000 mg/d) (SMD: 0·25, 95% CI 0·02, 0·49, P=0·043) and vitamin E alone (300-1800 IU/d; 1 IU vitamin E=0·67 mg natural vitamin E) (SMD: 0·48, 95% CI 0·23, 0·72, P=0·0001), whereas co-administration of both vitamins was ineffective (vitamin C: 500-2000 mg/d; vitamin E: 400-1200 IU/d) (SMD: 0·12, 95% CI-0·18, 0·42, P=0·428). The effect of vitamin C supplementation on EF increased significantly with age (β 0·023, 95% CI 0·001, 0·05, P=0·042). There was a significant negative correlation between baseline plasma vitamin E concentration and the effect of vitamin E supplementation on EF (β-0·03, 95% CI-0·06, -0·001, P=0·029). Supplementation with either vitamin C or vitamin E alone improves EF. However, subgroup analysis emphasises the importance of careful characterisation and selection of a population group which may benefit from such supplementation.

Topics: Adenosine Triphosphate; Adult; Aged; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Dietary Supplements; Endothelium, Vascular; Female; Humans; Inflammation; Male; Middle Aged; Mitochondria; Oxidative Stress; Randomized Controlled Trials as Topic; Reactive Oxygen Species; Regression Analysis; Vitamin E; Young Adult

Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Atrial Fibrillation; Cardiac Surgical Procedures; Colchicine; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Inflammation Mediators; Myocardial Reperfusion Injury; Oxidative Stress; Postoperative Complications; Reactive Oxygen Species; Risk Factors; Systemic Inflammatory Response Syndrome; Vitamin E

Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs.

Topics: Animals; Antioxidants; Ascorbic Acid; Chronic Disease; Humans; Immune System; Inflammation

Observational studies indicate that higher vitamin C intake is associated with reduced risk for cardiovascular diseases. However, randomised controlled trials (RCT) examining the effect of vitamin C on endothelial function (EF) have reported inconsistent results. The aims of this systematic review and meta-analysis were to determine the effect of vitamin C supplementation on EF and to investigate whether the effect was influenced by health status, study duration, dose and route of vitamin C administration.. We searched the Medline, Embase, Cochrane Library, and Scopus databases from inception to May 2013 for studies that met the following criteria: 1) RCT with adult participants, 2) vitamin C administered alone, 3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography and pulse wave analysis.. Pooling the data from 44 clinical trials showed a significant positive effect of vitamin C on EF (SMD: 0.50, 95% CI: 0.34, 0.66, P < 0.001). Stratification of the analysis by health outcome revealed improved EF in atherosclerotic (SMD: 0.84, 95% CI: 0.41, 1.26, P < 0.001), diabetic (SMD: 0.52, 95% CI: 0.21, 0.82, P < 0.001) and heart failure patients (SMD: 0.48, 95% CI: 0.08, 0.88, P < 0.02) after vitamin C supplementation. The effect size appeared to be unaffected by study design, duration, baseline plasma vitamin C concentration or route of administration of vitamin C. The meta-regression showed a significant positive association between vitamin C dose and improvement in EF (β: 0.00011, 95% CI: 0.00001, 0.00021, P = 0.03).. Vitamin C supplementation improved EF. The effect of vitamin C supplementation appeared to be dependent on health status, with stronger effects in those at higher cardiovascular disease risk. PROSPERO Database registration: CRD42013004567, http://www.crd.york.ac.uk/prospero/

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Atherosclerosis; Cardiovascular Diseases; Dietary Supplements; Endothelium; Female; Healthy Volunteers; Humans; Inflammation; Male; Middle Aged; Randomized Controlled Trials as Topic; Regression Analysis; Young Adult

Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC) status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM) affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

Topics: Adiposity; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Comorbidity; Humans; Inflammation; Life Style; Non-alcoholic Fatty Liver Disease; Nutritional Status; Obesity; Prevalence; Prognosis; Risk Assessment; Risk Factors

Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation.

Topics: Administration, Inhalation; Animals; Antioxidants; Ascorbic Acid; Brain; Carbon Tetrachloride; Carrageenan; Edema; Free Radicals; Gases; Inflammation; Mice; Radon; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase; Vitamin E; X-Rays

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the degeneration and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. It has been suggested that oxidative stress plays a role in the etiology and progression of PD. For instance, low levels of endogenous antioxidants, increased reactive species, augmented dopamine oxidation, and high iron levels have been found in brains from PD patients. In vitro and in vivo studies of Parkinson models evaluating natural and endogenous antioxidants such as polyphenols, coenzyme Q10, and vitamins A, C, and E have shown protective effects against oxidative-induced neuronal death. In this paper, we will review the mechanisms by which polyphenols and endogenous antioxidants can produce protection. Some of the mechanisms reviewed include: scavenging nitrogen and oxygen reactive species, regulation of signaling pathways associated with cell survival and inflammation, and inhibition of synphilin-1 and alpha-synuclein aggregation.

Topics: alpha-Synuclein; Animals; Antioxidants; Ascorbic Acid; Carrier Proteins; Cell Death; Dopamine; Dopaminergic Neurons; Humans; Inflammation; Nerve Tissue Proteins; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; Polyphenols; Reactive Oxygen Species; Signal Transduction; Substantia Nigra; Ubiquinone; Vitamin A; Vitamin E

As explained in the first part of the article, vitamins and trace elements influence various metabolic functions that are directly related to immune function. In this context, secosteroid vitamin D has met with growing interest. The discussion has focused on whether and, if so, to what extent, vitamin D might contribute to the prevention and possibly the treatment of infections and autoimmune diseases. We know, for instance, that immune cells are capable of synthesizing calcitriol from its precursor calcidiol, whereby the former enhances the synthesis of antibacterial peptides by macrophages while simultaneously inhibiting the (auto)immune response mediated by T helper cells (Th1). Numerous observational studies support the hypothesis that a vitamin D deficit increases the risk of autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis, psoriasis and rheumatoid arthritis; however, there are few reliable interventional studies to date. In general, immune status represents a sensitive indicator of micronutrient supply. Conversely, the activity of the immune system has an effect on the status of and requirements for nutrients.

Topics: Animals; Ascorbic Acid; Autoimmunity; Communicable Diseases; Dietary Supplements; Ergocalciferols; Humans; Immune System; Inflammation; Inflammation Mediators; Signal Transduction; Vitamin D Deficiency

As elements of the antioxidant system, cofactors of enzymes, components of transcription factors, and epigenetic modulators, micronutrients, such as vitamins and trace elements, influence various metabolic processes that are directly associated with immune functions. Specifically, the vitamins C and D have been shown to have significance immune function. Therefore, the objective of this review is to elucidate interactions between micronutrients and the immune system. In the initial section of this review, we present a general overview of interactions between the immune system and micronutrients, with a focus on the immunobiologically relevant functions of vitamin C. Immune competent cells accumulate vitamin C against a concentration gradient, with a close relationship between vitamin C supply and immune cell activity, especially phagocytosis activity and T-cell function. Accordingly, one of the consequences of vitamin C deficiency is impaired resistance to various pathogens, while an enhanced supply increases antibody activity and infection resistance.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Communicable Diseases; Dietary Supplements; Ergocalciferols; Humans; Immune System; Inflammation; Inflammation Mediators; Signal Transduction

Kiwifruit are nutrient-dense fruit with a reputation for promoting good health. Although this could be attributed to the high vitamin C content of kiwifruit, other phytochemicals could also provide health benefits. Kiwifruit are commonly reported to be a good source of vitamin E and in addition contain phenolics and carotenoids. The antioxidant properties of kiwifruit have received attention as possible mechanisms for their health-promoting effects. In this review, the antioxidant capacity of kiwifruit is discussed in the context of biologically relevant in vitro assays for predicting antioxidant activity in a biological setting compared with chemical antioxidant assays, and the ability of kiwifruit to protect cells from dying after exposure to an oxidative insult by hydrogen peroxide (cytoprotection). Some recent data are included, where extracts from twenty kiwifruit genotypes, derived from germplasm held at The New Zealand Institute for Plant & Food Research Ltd, were compared for their cellular antioxidant activity and cytoprotection, using human gut-derived epithelial cell lines. Our knowledge of how this type of result is currently reflected in vivo is summarised, together with the 'naturally protective' properties of kiwifruit that involve modulating immune responses in a positive way. Finally, the ways in which these antioxidant and natural protective properties of kiwifruit may influence human health and wellness are discussed.

Topics: Actinidia; Animals; Antioxidants; Ascorbic Acid; Biological Assay; Carotenoids; Cell Line; Cytoprotection; Epithelial Cells; Flavonoids; Fruit; Humans; Hydrogen Peroxide; Immunity; Inflammation; Intestines; Mice; New Zealand; Oxidation-Reduction; Phenols; Plant Extracts; Polyphenols; Vitamin E

The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections, and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid-soluble antioxidant, scavenging hydroperoxyl radicals in a lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, by vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review.

Topics: Animals; Antioxidants; Ascorbic Acid; Cytoprotection; Energy Metabolism; Free Radicals; Humans; Hypoxia-Inducible Factor 1; Inflammation; Neoplasms; Randomized Controlled Trials as Topic; Vitamin E

Intracellular and extracellular oxidative stress initiated by reactive oxygen species (ROS) advance skin aging, which is characterized by wrinkles and atypical pigmentation. Because UV enhances ROS generation in cells, skin aging is usually discussed in relation to UV exposure. The use of antioxidants is an effective approach to prevent symptoms related to photo-induced aging of the skin. In this review, the mechanisms of ROS generation and ROS elimination in the body are summarized. The effects of ROS generated in the skin and the roles of ROS in altering the skin are also discussed. In addition, the effects of representative antioxidants on the skin are summarized with a focus on skin aging.

Topics: Aging; Antioxidants; Ascorbic Acid; Carotenoids; Flavonoids; Humans; Inflammation; Models, Biological; Oxidative Stress; Phenols; Polyphenols; Reactive Oxygen Species; Sebaceous Glands; Skin; Skin Aging; Ultraviolet Rays; Vitamin E

Chronic inflammation is a pathogenic feature of atherosclerosis and cardiovascular disease mediated by substances including angiotensin II, proinflammatory cytokines, and free fatty acids. This promotes generation of reactive oxygen species in vascular endothelial cells and smooth muscle cells, which mediate injury through several mechanisms. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidaemia and the renin-angiotensin-aldosterone system (RAAS) at multiple levels contribute importantly to a variety of risk factors. Therefore, combination therapy that simultaneously addresses multiple mechanisms for the pathogenesis of atherosclerosis is an attractive emerging concept for slowing progression of atherosclerosis. Combined therapy with statins, peroxisome proliferator-activated receptors, and RAAS blockade demonstrates additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors due to both distinct and interrelated mechanisms. These additive beneficial effects of combined therapies are consistent with laboratory and recent clinical studies. Thus, combination therapy may be an important paradigm for treating and slowing progression of atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Atherosclerosis; Calcium Channel Blockers; Cardiovascular Agents; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Insulin Resistance; NADPH Oxidases; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Reactive Oxygen Species; Renin-Angiotensin System; Treatment Outcome; Vitamin E

A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome.. Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery.. These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Cells; Critical Illness; Fatty Acids, Omega-3; Glutamine; Heat-Shock Proteins; Humans; Inflammation; Microcirculation; Micronutrients; Selenium; Zinc

Parenteral ascorbic acid has been frequently used to overcome problems of vitamin C deficiency in haemodialysis patients. The benefits of vitamin C supplementation in clinical studies have been controversial and did not consider toxicological aspects. The review summarizes recent findings of the effects of parenteral ascorbic acid and discusses toxicological effects.. Vitamin C deficiency in haemodialysis patients, which has been frequently described, cannot be improved with oral supplementation due to limited absorption of high dosages. To avoid consequences of vitamin C deficiency, parenteral vitamin C solutions should be administered because this intervention is the only way to guarantee a sufficient supply to the cells. A beneficial consequence of parenteral vitamin C on the recombinant human erythropoietin resistance is an additional therapeutic effect, which contributes to the prevention of iron deficiency anaemia in haemodialysis patients. Thus, large amount of supplemental vitamin C are required for extended periods of time (up to 500 mg 3 times a week). To avoid hyperoxaluria, plasma oxalate levels should be monitored on a regular basis, for example, once a week.. Parenteral administration of ascorbic acid may be an approach that can overcome problems of vitamin C deficiency in haemodialysis patients - in particular problems of iron overload, erythropoetin resistance, and chronic inflammation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Drug Resistance; Erythropoietin; Hemosiderosis; Humans; Inflammation; Infusions, Parenteral; Renal Dialysis

Oxidative reactions caused by cigarette smoke (CS) chemicals have been shown to initiate crucial events in atherogenesis. However, physicians and scientists are confronted with the paradoxical situation that an antioxidative treatment of smokers improves acute smoking effects but hardly has any impact on long term outcome of cardiovascular diseases (CVD). In this review we make an attempt to explain this paradox. First, smoke-derived free radicals and oxidants are part of CS causing a pro-oxidative state in the circulatory system. Further, smoke chemicals down-regulate antioxidant defence enzymes that would counteract the oxidative burden by cigarette smoke. With the prolonged exposure to smoke, oxidation catalysing metals accumulate in the vessel wall and mediate local oxidation reactions. Therefore, pharmacological intervention relying on non-selective antioxidants often appears to be ineffective. Consequently a novel strategy for the prevention and treatment of CVD caused by smoking is suggest, relying on a combined application of antioxidants, substitution of factors important for physiological oxidant defence, and metal-detoxifying agents.

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Calcium; Cardiovascular Diseases; Humans; Inflammation; Oxidants; Oxidative Stress; Smoking; Vitamin E

Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.

Topics: Antioxidants; Ascorbic Acid; Humans; Immune System; Immunity, Active; Immunity, Innate; Infection Control; Inflammation; Oxidation-Reduction; Oxidative Stress; Zinc

The systemic inflammatory response syndrome results from an uncontrolled, overexpression of the normal host inflammatory response, leading to destruction of host tissue and subsequent organ failure. Oxidant stress has been implicated in this process both as a mechanism for direct cellular injury, as well as activation of intracellular signaling cascades within inflammatory cells resulting in progression of the inflammatory response. Vitamin E is an inexpensive, nontoxic, chain-breaking antioxidant that has therapeutic potential in regulating this process. This review seeks to evaluate the current literature regarding the use of Vitamin E in controlling the excessive inflammation seen in systemic inflammatory response syndrome and argues for further study of its therapeutic potential for these critically ill patients.

Topics: Acute Disease; alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Infant, Newborn; Inflammation; Models, Biological; Models, Chemical; Multiple Organ Failure; Respiratory Distress Syndrome, Newborn; Systemic Inflammatory Response Syndrome; Vitamin E

Microparticles are membrane vesicles released from many different cell types. There are two mechanisms that can result in their formation, cell activation and apoptosis. In these two mechanisms, different pathways are involved in microparticle generation. Microparticle generation seems to be a well regulated process. Microparticles vary in size, phospholipid and protein composition. They have a potent pro-inflammatory effect, promote coagulation and affect vascular function. Since these processes are all involved in the pathogenesis of cardiovascular disease and circulating microparticle numbers are altered in many cardiovascular diseases, a role for microparticles in the pathogenesis of cardiovascular diseases is likely. Although hard evidence for a role of microparticles in cardiovascular diseases at present is still only limited, new evidence is accumulating rapidly to support this theory. Elucidation of the microparticle composition and the mechanisms involved in exertion of their effects will supply this evidence and enable us to develop additional intervention strategies for prevention and treatment of cardiovascular diseases.

Topics: Abciximab; Antibodies, Monoclonal; Anticoagulants; Antioxidants; Apoptosis; Ascorbic Acid; Blood Coagulation; Blood Platelets; Calcium; Calcium Channel Blockers; Cardiovascular Diseases; Endothelium, Vascular; Female; Humans; Immunoglobulin Fab Fragments; Inflammation; Lipid Metabolism; Male; Membrane Lipids; Platelet Activation; Subcellular Fractions

Dehydroascorbic acid (DHA) is abundant in the human diet and also is generated from vitamin C (ascorbic acid, AA) in the lumen of the gastrointestinal tract. DHA is absorbed from the lumen of the small intestine and reduced to AA, which subsequently circulates in the blood. Utilization of AA as an antioxidant and enzyme cofactor causes its oxidation to DHA in extracellular fluid and cells. DHA has an important role in many cell types because it can be used to regenerate AA. Both physiological (e.g. insulin, insulin-like growth factor I, cyclic AMP) and pathological (e.g. oxidative stress, diabetes, sepsis) factors alter the transport and metabolic mechanisms responsible for this DHA recycling.

Topics: Animals; Ascorbic Acid; Biological Transport; Dehydroascorbic Acid; Diabetes Mellitus; Humans; Inflammation; Oxidation-Reduction; Reperfusion Injury; Sepsis

Information suggests that there may be gender-based differences in skeletal muscle responses to damaging exercise. Evidence demonstrates that estrogen has strong antioxidant properties and may be an important factor in maintaining postexercise membrane stability and limiting creatine kinase (CK) leakage from damaged muscle in female animals. Research demonstrates effects of estrogen and possible gender differences in other morphological and biochemical indices of postexercise muscle damage and leukocyte invasion. Nevertheless, there are conflicting findings suggesting that in some in vivo exercise models, estrogen administration has limited ability to affect exercise-induced oxidative stress and muscle damage and may cause loss of tissue vitamin C. Gender differences appear to exist in tissue levels of other important antioxidants such as vitamin E and glutathione. More research is needed to fully define the potential for estrogen to influence postexercise muscle damage and the inflammatory response and to determine the mechanisms by which it may operate.

Topics: Animals; Antioxidants; Ascorbic Acid; Creatine Kinase; Estrogens; Exercise; Female; Humans; Inflammation; Male; Muscle, Skeletal; Neutrophils; Oxidative Stress; Physical Conditioning, Animal; Sex Characteristics; Vitamin E

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

Topics: Animals; Antioxidants; Antiviral Agents; Ascorbic Acid; Blood Platelets; Coronary Disease; Cytoprotection; Enzyme Inhibitors; Flavonoids; Heart Diseases; Humans; Immune System; Inflammation; Lymphocytes; Mast Cells; Neoplasms; Xenobiotics

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Cardiovascular System; Female; Histamine; Histamine Antagonists; Humans; Hypersensitivity; Inflammation; Male; Rats

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Sickle Cell; Animals; Antioxidants; Arachidonic Acid; Ascorbic Acid; Cells, Cultured; Child; Endotoxins; Fetus; Free Radicals; Glomerulonephritis; Humans; Infections; Inflammation; Iron; Malaria; Mice; Oxidative Stress; Phagocytosis; Rabbits; Respiratory Distress Syndrome; Sheep

Routinely measuring iron status is necessary because not only are about 6% of Americans in significant negative iron balance, but about 1% have iron overload. Serum ferritin is in equilibrium with body iron stores, and is the only blood test that measures them. Barring inflammation, each one ng (0.0179 pmol) ferritin/ml of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early Stage I positive balance is best recognized by measuring saturation of iron binding capacity. Conversely, serum ferritin best recognizes early (Stage I and II) negative balance. Deviations from normal are: 1. Both stages of iron depletion (i.e. low stores, no dysfunction). Negative iron balance Stage I is reduced iron absorption producing moderately depleted iron stores. Stage II is severely depleted stores, without dysfunction. These stages include over half of all cases of negative iron balance. Treated with iron, they never progress to dysfunction, i.e. to disease. 2. Both stages of iron deficiency. Deficiency is inadequate iron for normal function, i.e. dysfunction, disease. Negative balance Stage III is dysfunction without anemia; Stage IV is with anemia. 3. Positive iron balance: Stage I is a multi-year period without dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction (disease). Iron removal prevents progression. Stage II is iron overload disease, encompassing years of insidiously progressive damage to tissues and organs from iron overload. Iron removal arrests progression.

Topics: Adolescent; Adult; Anemia, Hypochromic; Ascorbic Acid; Child; Child, Preschool; Cost-Benefit Analysis; Female; Ferritins; Folic Acid Deficiency; Gene Frequency; Genetic Predisposition to Disease; Hemochromatosis; HLA-A3 Antigen; Humans; Incidence; Infant; Inflammation; Iron; Iron Deficiencies; Male; Middle Aged; Pregnancy

Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs.

Topics: Animals; Arthritis, Rheumatoid; Ascorbic Acid; Autoimmune Diseases; Ceruloplasmin; Chemotactic Factors; Cricetinae; Cricetulus; Free Radicals; Humans; Immune Complex Diseases; Inflammation; Lipid Peroxides; Myocardial Infarction; NADH, NADPH Oxidoreductases; NADPH Oxidases; Neutrophils; Oxidation-Reduction; Oxygen; Pancreatic Elastase; Peroxidase; Peroxidases; Peroxides; Phagocytosis; Pulmonary Emphysema; Respiratory Distress Syndrome; Superoxide Dismutase; Superoxides; Vasculitis; Vitamin E

A review of the literature relating to possible clinical implications of ascorbic acid (AA) supplementation was conducted. Factors requiring a higher AA intake include smoking, alcohol ingestion, stress, diabetes mellitus, pregnancy, and certain drugs, including oral contraceptives, some antibiotics, acetylsalicylate and anti-inflammatory medications. AA has been found to significantly increase wound healing, reduce the inflammatory response, lessen respiratory distress, enhance immune function and serve to benefit many common conditions including osteoarthritis. It is concluded that vitamin C supplementation could be utilized for many conditions seen by chiropractors.

Topics: Age Factors; Alcoholism; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ascorbic Acid; Aspirin; Chiropractic; Contraceptives, Oral; Diet; Drug Interactions; Female; Fruit; Humans; Immunity; Inflammation; Nutritional Requirements; Pregnancy; Respiratory Tract Diseases; Smoking; Stress, Physiological; Wound Healing

Topics: Animals; Ascorbic Acid; Candida albicans; Cell Division; Chemotaxis, Leukocyte; Copper; Cyclic GMP; Extracellular Matrix; Extracellular Space; Histamine; Horseradish Peroxidase; Humans; Hydrogen Peroxide; Hypersensitivity; Immunization; Inflammation; Iodides; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Phagocytosis; Prostaglandins; SRS-A

All leukocytes are capable of responding chemotactically (oriented locomotion) and chemokinetically (stimulated nondirected or random locomotion) to a variety of chemical agents. A brief review of the in vitro and in vivo methods of studying neutrophil movement and our present knowledge of chemotactic factors is presented as well as a discussion on the mechanisms of stimulated movement. Two clinically important instances of defects in neutrophil movement, ie, the Chédiak-Higashi syndrome and a case of actin dysfunction, are herein described.

Topics: Ascorbic Acid; Calcium; Cell Movement; Chediak-Higashi Syndrome; Chemotaxis, Leukocyte; Complement C3; Complement C5; Cyclic AMP; Cyclic GMP; Cytological Techniques; Cytoskeleton; Humans; Inflammation; Kallikreins; Lysosomes; Microtubules; Neutrophils; Oligopeptides; Plasminogen Activators; Receptors, Drug; Skin Window Technique; Sodium; Structure-Activity Relationship

Topics: Acid-Base Equilibrium; Adenosine Triphosphatases; Anti-Inflammatory Agents; Ascorbic Acid; Autacoids; Chloroquine; Glycosaminoglycans; Gold; Histamine H1 Antagonists; Humans; Hydrogen-Ion Concentration; Indomethacin; Inflammation; Phenylbutazone; Salicylates; Salts

Topics: Ascorbic Acid; Carbon Isotopes; Chemistry Techniques, Analytical; Chondroitin; Collagen; Glycosaminoglycans; Granuloma; Hexosamines; Histocytochemistry; Hyaluronic Acid; Hypersensitivity; Inflammation; Proteins; Research; Sulfur Isotopes

We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p < 0.01) and 12 weeks (p < 0.05) and serum adiponectin after 3 weeks (p < 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.

Topics: Adipokines; Adiponectin; Antioxidants; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Obesity; Overweight; Plant Extracts; Polyesters; Telomere

Circulating interleukin (IL)-6 and IL-10 concentrations can be elevated following the surgically induced trauma of total knee arthroplasty (TKA). An exaggerated increase in IL-6 relative to IL-10 (i.e., IL-6/IL-10 ratio) associates with trauma severity and indicative of pro-inflammatory predominance. Although various vitamins and minerals alter individual IL-6 and IL-10 concentrations in the blood, surprisingly, it is unknown if a multi-vitamin supplement alters the IL-6/IL-10 ratio during the systemic inflammatory response following TKA. The objective of this study was to identify if a multi-vitamin with mineral supplement taken prior to alters the circulating IL-6/IL-10 ratio following total knee arthroplasty (TKA). This study consisted of a randomized, double-blind, placebo controlled design. Twenty-one subjects undergoing elective, primary, unilateral TKA were randomly assigned to a placebo (PL, n = 11) or multi-vitamin with mineral supplement (MV, n = 10). Supplements were taken daily starting approximately 6-weeks prior to surgery. Supplements were not taken the day of surgery or during inpatient care 2-days after surgery. Circulating IL-6, IL-10, high-sensitivity CRP (hsCRP), vitamin C (ascorbic acid (AA)), vitamin D (25-hydroxyvitamin D (25(OH)D)), and vitamin E (α-tocopherol (αT)) concentrations were measured in fasting blood draw samples obtained ~6-weeks prior to surgery (and before starting supplementation), the morning of surgery, and 24-hours and 48-hours after surgery. MV supplementation tended to increase serum 25(OH)D and significantly increased plasma AA and plasma αT before surgery without mitigating the post-operative IL-6 and hsCRP increases. However, the post-operative increase in the serum IL-6/IL-10 ratio after surgery was significantly blunted in the MV group. Based on these findings, we conclude that a multi-vitamin with mineral supplement taken daily for several weeks before surgery might reduce the pro-inflammatory predominance after TKA. Future research confirming or refuting the novel data presented herein is needed.

Topics: alpha-Tocopherol; Arthroplasty, Replacement, Knee; Ascorbic Acid; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Pilot Projects; Vitamin D

To evaluate gingival inflammation from fixed-dose combinations of vitamin C, vitamin E, lysozyme and carbazochrome (CELC) in the treatment of chronic periodontitis following scaling and root planing.. One hundred patients were randomly assigned to receive CELC (test) or placebo (control) for the first 4 weeks at a 1:1 ratio, and both groups received CELC for the remaining 4 weeks. Primary outcome was the mean change in the gingival index (GI) after 4 weeks. Secondary outcomes included mean change in GI after 8 weeks and plaque index, probing depth, clinical attachment level, and VAS at 4 weeks and 8 weeks.. Ninety-three patients completed the study. The GI in the test group significantly decreased after 4 weeks (p < 0.001) and 8 weeks (p < 0.001). The mean change from baseline in GI significantly decreased in the test group compared to the control group after 4 weeks (p = 0.015). In the GEE model adjusting for age, gender and visits, the test group showed 2.5 times GI improvement compared to the control group (p = 0.022).. Within the study, CELC showed a significant reduction in gingival inflammation compared with a placebo. Other parameters, however, were similar between groups.. KCT0001366 (Clinical Research Information Service, Republic of Korea) and 29 Jan 2015, retrospectively registered.

Topics: Adrenochrome; Anti-Bacterial Agents; Ascorbic Acid; Chronic Periodontitis; Dental Plaque Index; Dental Scaling; Double-Blind Method; Drug Therapy, Combination; Gingival Crevicular Fluid; Humans; Inflammation; Muramidase; Republic of Korea; Retrospective Studies; Root Planing; Vitamin E

Antioxidants have been reported to have anti-inflammatory effects, but there is a lack of research comparing food to supplement antioxidant sources. The aim of this study was to determine if increases in intake of foods naturally rich in antioxidants would lower blood levels of inflammatory markers more than consuming antioxidant supplements among adults with cardiovascular disease risk factors. Eighty-eight generally healthy adults with ≥1 elevated risk factor for cardiovascular disease were randomized in a single-blind (diets)/double-blind (supplements), parallel-group study for 8 weeks. Participants consumed (1) usual diet and placebo pills (n = 29), (2) usual diet and antioxidant supplements (n = 29), or (3) antioxidant-rich foods closely matched to antioxidant content of supplements and placebo (n = 30). Usual diet combined with antioxidant supplements or increased antioxidant-rich food intake was designed to approximately double daily habitual antioxidant intake. Antioxidant pills included carotenoids, mixed tocopherols, vitamin C, and selenium. Fasting blood samples were analyzed for inflammatory marker concentrations of interleukin-6, monocyte chemotactic protein-1, and soluble intercellular adhesion molecule-1. Participants in the intervention groups successfully doubled most antioxidants as verified by diet records and elevated blood concentrations in treatment groups. Baseline levels of inflammatory markers for the entire study group were 110 ± 65 pg/mL for monocyte chemotactic protein-1, 0.9 ± 0.7 pg/mL for interleukin-6, and 217 ± 56 ng/mL for soluble intercellular adhesion molecule-1 (means ± standard deviation) and did not differ by treatment arm. After 8 weeks, there were no significant within-group changes or between-group 8-week change differences in inflammatory marker concentrations. In conclusion, no beneficial effects were detected on the inflammatory markers investigated in response to antioxidants from foods or supplements.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Biomarkers; Cardiovascular Diseases; Carotenoids; Chemokine CCL2; Diet; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Pilot Projects; Selenium; Single-Blind Method; Tocopherols; Vitamins

Objective Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system. Methods An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications. Results Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C. Conclusions Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases.. Clinical Trials NCT02422901.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Antioxidants; Ascorbic Acid; Child; Female; Humans; Hypersensitivity; Inflammation; Male; Middle Aged; Oxidative Stress; Prospective Studies; Young Adult

The aim of this pilot study was to investigate the effects of four weeks of an oral health optimized diet on periodontal clinical parameters in a randomized controlled trial.. The experimental group (n = 10) had to change to a diet low in carbohydrates, rich in Omega-3 fatty acids, and rich in vitamins C and D, antioxidants and fiber for four weeks. Participants of the control group (n = 5) did not change their dietary behavior. Plaque index, gingival bleeding, probing depths, and bleeding upon probing were assessed by a dentist with a pressure-sensitive periodontal probe. Measurements were performed after one and two weeks without a dietary change (baseline), followed by a two week transitional period, and finally performed weekly for four weeks.. Despite constant plaque values in both groups, all inflammatory parameters decreased in the experimental group to approximately half that of the baseline values (GI: 1.10 ± 0.51 to 0.54 ± 0.30; BOP: 53.57 to 24.17 %; PISA: 638 mm(2) to 284 mm(2)). This reduction was significantly different compared to that of the control group.. A diet low in carbohydrates, rich in Omega-3 fatty acids, rich in vitamins C and D, and rich in fibers can significantly reduce gingival and periodontal inflammation.. German Clinical Trials Register; https://www.germanctr.de (DRKS00006301). Registered on 2015-02-21.

Topics: Ascorbic Acid; Dental Plaque; Dental Plaque Index; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Gingivitis; Humans; Inflammation; Oral Health; Periodontal Index; Pilot Projects; Vitamin D

Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplementation with anti-oxidants is potentially beneficial for CF patients.. The effect of 4 weeks of oral N-acetylcysteine (NAC) treatment (2400 mg/day divided into two doses) on biochemical parameters of oxidative stress was investigated in an open-label, controlled, randomized trial on 21 patients; 11 patients in the NAC group and 10 in the control group. Biochemical parameters of oxidative burden and plasma levels of antioxidants were assessed at the end of the study and compared to the baseline values in the two groups.. A significant increase in the plasma levels of the antioxidant ascorbic acid (p=0.037) and a significant decrease in the levels of the oxidized form of ascorbic acid (dehydroascorbate) (p=0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change significantly compared to baseline in either of the groups. A better lung function was observed in the NAC treated group with a mean (SD) change compared to baseline of FEV1% predicted of 2.11 (4.6), while a decrease was observed in the control group (change -1.4 (4.6)), though not statistically significant.. Treatment with N-acetylcysteine 1200 mg×2/day for 30 days significantly decreased the level of oxidized vitamin C and increased the level of vitamin C (primary end-points) and a not statistically significant improvement of lung function was observed in this group of patients.

Topics: Acetylcysteine; Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Chronic Disease; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Forced Expiratory Volume; Humans; Inflammation; Lung; Male; Middle Aged; Oxidative Stress; Pseudomonas Infections; Reactive Oxygen Species; Treatment Outcome

An improvement in oxidative status is associated with a reduction in the incidence of several chronic diseases. However, daily intake of antioxidants in Western diets is decreasing. This study evaluates the effect of daily consumption of an antioxidant-rich juice (ARJ) on oxidative status, cardiovascular disease risk parameters, and untargeted plasma and urine metabolomes. Twenty-eight healthy young adults participated in an 8-week clinical trial by drinking 200 mL of ARJ (pomegranate and grape) daily. At the end of the study, the subjects showed a significant decrease (-29%) in plasma lipid oxidation (malondialdehyde concentration), and a significant increase (+115%) in plasma antioxidant capacity. Plasma and urine metabolomes were also significantly modified and some ions modified in urine were identified, including metabolites of polyphenols, ascorbic acid and biliary acids. No significant changes were observed in lipid profile, inflammation, blood pressure or glycaemia. These results show that incorporating antioxidant-rich beverages into common diets may improve oxidative status in healthy subjects.

Topics: Adult; Antioxidants; Ascorbic Acid; Beverages; Blood Glucose; Blood Pressure; Female; Fruit; Humans; Inflammation; Lipids; Lythraceae; Male; Malondialdehyde; Metabolome; Oxidative Stress; Polyphenols; Vitis

We studied the effects of diet supplementation with docosahexaenoic (DHA) and in vitro vitamin C (VitC) at physiological concentrations on oxidative and inflammatory neutrophil response to phorbol myristate acetate (PMA). Fifteen male footballers ingested a beverage enriched with DHA or a placebo for 8 weeks in a randomized double-blind study. Neutrophils were isolated from blood samples collected in basal conditions at the end of nutritional intervention. Neutrophils were cultured for 2 hours at 37°C in (a) control media, (b) media with PMA, and (c) media with PMA + VitC. PMA induces neutrophil degranulation with increased extracellular myeloperoxidase and catalase activities, nitric oxide production, expression of the inflammatory genes cyclooxygenase-2, nuclear factor κβ, interleukin 8 and tumor necrosis factor α, and interleukin 6 production. DHA diet supplementation boosts the exit of CAT from neutrophils but moderates the degranulation of myeloperoxidase granules induced by PMA. VitC facilitates azurophilic degranulation of neutrophils and increases gene expression of myeloperoxidase induced by PMA. VitC and DHA diet supplementation prevent PMA effects on inflammatory gene expression, although together they do not produce additional effects. DHA diet supplementation enhances antioxidant defences and anti-inflammatory neutrophil response to in vitro PMA activation. VitC facilitates neutrophil degranulation but prevents an inflammatory response to PMA.

Topics: Ascorbic Acid; Catalase; Dietary Supplements; Docosahexaenoic Acids; Erythrocytes; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Male; Neutrophil Activation; Neutrophils; Nitrates; Nitrites; Oxidative Stress; Peroxidase; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha; Young Adult

Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.. FPSK_Mac [13]04.. The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults.. Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day.. In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.. Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypertension; Inflammation; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Obesity; Time Factors; Treatment Outcome; Triglycerides; Young Adult

Safe systemic protection from the health hazards of ultraviolet radiation (UVR) in sunlight is desirable. Green tea is consumed globally and is reported to have anti-inflammatory properties, which may be mediated through the impact on cyclooxygenase and lipoxygenase pathways. Recent data suggest that green tea catechins (GTCs) reduce acute UVR effects, but human trials examining their photoprotective potential are scarce.. We performed a double-blind, randomized, placebo-controlled trial to examine whether GTCs protect against clinical, histologic, and biochemical indicators of UVR-induced inflammation.. Healthy adults (aged 18-65 y, phototypes I-II) were randomly allocated to 1350 mg encapsulated green tea extract (540 mg GTC) with 50 mg vitamin C or placebo twice daily for 3 mo. Impact on skin erythema, dermal leukocytic infiltration, and concentrations of proinflammatory eicosanoids was assessed after solar-simulated UVR challenge, and subject compliance was determined through assay of urinary GTC metabolite epigallocatechin glucuronide.. Volunteers were assigned to the active (n = 25) or the placebo (n = 25) group. After supplementation, median (IQR) sunburn threshold (minimal erythema dose) was 28 (20-28) and 20 (20-28) mJ/cm(2) in the active and placebo groups, respectively (nonsignificant), with no difference in AUC analysis for measured erythema index after a geometric series of 10 UVR doses. Skin immunohistochemistry showed increased neutrophil and CD3(+) T-lymphocyte numbers post-UVR in both groups (P < 0.01) with no statistically significant differences between groups after supplementation. Cyclooxygenase and lipoxygenase metabolites prostaglandin E2 (vasodilator) and 12-hydroxyeicosatetraenoicacid (chemoattractant), respectively, increased after UVR (P < 0.05), with no differences between supplementation groups.. Oral GTC (1080 mg/d) with vitamin C over 3 mo did not significantly reduce skin erythema, leukocyte infiltration, or eicosanoid response to UVR inflammatory challenge. This trial was registered at clinicaltrials.gov as NCT01032031.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Catechin; Dietary Supplements; Dinoprostone; Dose-Response Relationship, Drug; Double-Blind Method; Erythema; Female; Humans; Inflammation; Male; Middle Aged; Skin; Sunburn; Tea; Ultraviolet Rays; Young Adult

Many patients each year require prolonged mechanical ventilation. Inflammatory processes may prevent successful weaning, and evidence indicates that mechanical ventilation induces oxidative stress in the diaphragm, resulting in atrophy and contractile dysfunction of diaphragmatic myofibers. Antioxidant supplementation might mitigate the harmful effects of the oxidative stress induced by mechanical ventilation.. To test the clinical effectiveness of antioxidant supplementation in reducing the duration of mechanical ventilation.. A randomized, prospective, placebo-controlled double-blind design was used to test whether enterally administered antioxidant supplementation would decrease the duration of mechanical ventilation, all-cause mortality, and length of stay in the intensive care unit and hospital. Patients received vitamin C 1000 mg plus vitamin E 1000 IU, vitamin C 1000 mg plus vitamin E 1000 IU plus N-acetylcysteine 400 mg, or placebo solution as a bolus injection via their enteral feeding tube every 8 hours.. Clinical and statistically significant differences in duration of mechanical ventilation were seen among the 3 groups (Mantel-Cox log rank statistic = 5.69, df = 1, P = .017). The 3 groups did not differ significantly in all-cause mortality during hospitalization or in the length of stay in the intensive care unit or hospital.. Enteral administration of antioxidants is a simple, safe, inexpensive, and effective intervention that decreases the duration of mechanical ventilation in critically ill adults.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Critical Care; Critical Illness; Cystine; Double-Blind Method; Female; Humans; Inflammation; Length of Stay; Male; Middle Aged; Oxidative Stress; Prospective Studies; Respiration, Artificial; Time Factors; Treatment Outcome; Vitamin E; Vitamins

Postprandial stress induced by acute consumption of meals with a high fat content results in an increase of markers of cardiometabolic risk. Repeated acute dietary stress may induce a persistent low-grade inflammation, playing a role in the pathogenesis of functional gut diseases. This may cause an impairment of the complex immune response of the gastrointestinal mucosa, which results in a breakdown of oral tolerance. We investigated the effect of ingestion of a fruit-juice drink (FJD) composed by multiple fruit juice and extracts, green tea extracts and vitamin C on postprandial stress induced by a High Fat Meal (HFM) in healthy overweight subjects. Following a double blind, placebo controlled, cross-over design, 15 healthy overweight subjects were randomized to a HFM providing 1334 Kcal (55% fat, 30% carbohydrates and 15% proteins) in combination with 500 mL of a placebo drink (HFM-P) or a fruit-juice drink (HFM-FJD). Ingestion of HFM-P led to an increase in circulating levels of cholesterol, triglycerides, glucose, insulin, TNF-α and IL-6. Ingestion of HFM-FJD significantly reduced plasma levels of cholesterol and triglycerides, decreasing inflammatory response mediated by TNF-α and IL-6. Ingestion of a fruit-juice drink reduce markers of postprandial stress induced by a HFM.

Topics: Adult; Ascorbic Acid; Beverages; Blood Glucose; Cross-Over Studies; Dietary Fats; Double-Blind Method; Female; Fruit; Humans; Inflammation; Insulin; Interleukin-6; Lipids; Male; Middle Aged; Overweight; Postprandial Period; Tumor Necrosis Factor-alpha

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [β = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081.

Topics: Adolescent; Alanine Transaminase; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Biomarkers; Child; Dietary Supplements; Female; gamma-Glutamyltransferase; Humans; Inflammation; Inflammation Mediators; Isoprostanes; Liver; Liver Function Tests; Male; Micronutrients; Obesity; Oxidative Stress; Selenium; Weight Reduction Programs

The effects of the DASH (Dietary Approaches to Stop Hypertension) diet on inflammation in childhood metabolic syndrome (MetS) have still to be identified.. To examine the effects of the DASH diet on markers of systemic inflammation in adolescents with MetS.. In this randomized, cross-over clinical trial, 60 postpubescent girls with MetS were randomly assigned to receive either the DASH diet menu cycles or usual dietary advice (UDA) for 6 weeks. After a 4-week washout period, participants were crossed over to the alternate arm. The DASH diet was designed to maintain the current body weight. This diet contained high amounts of fruit, vegetables and low-fat dairy products and was low in saturated fats and cholesterol. UDA consisted of general oral advice and written information about healthy food choices based on the Healthy Eating Plate. Compliance to the DASH diet was assessed through quantification of plasma vitamin C levels. Fasting venous blood samples were taken 4 times from each participant: at baseline and at the end of each study arm. Circulating levels of biomarkers of systemic inflammation were quantified according to standard protocols.. Mean (SD) age and weight of participants was 14.2 years (1.7) and 69 kg (14.5), respectively. Serum vitamin C levels tended to increase during the DASH phase compared with the UDA phase (16.8 ± 12.9 vs. -13.8 ± 9.7 ng/dl, respectively, p = 0.06) indicating a relatively good compliance to the DASH diet. Adherence to the DASH diet, compared to the UDA, had a significant effect on serum high-sensitivity C-reactive protein levels (p = 0.002). This effect remained significant even after adjustment for weight changes and after further controlling for changes in lipid profiles. We did not observe any significant effect of intervention on levels of serum tumor necrosis factor-alpha, interleukin (IL)-2, IL-6 and adiponectin, in either the crude or adjusted models. There were no significant group*time interactions for any dependent variable, except for IL-6; this was close to the significant level.. In summary, consumption of the DASH eating pattern for 6 weeks may reduce circulating levels of hs-CRP among adolescents with MetS. Other inflammatory markers were not affected by the DASH diet.

Topics: Adiponectin; Adolescent; Ascorbic Acid; Biomarkers; Body Weight; C-Reactive Protein; Child; Cross-Over Studies; Dairy Products; Diet; Fatty Acids; Female; Fruit; Humans; Inflammation; Interleukin-2; Interleukin-6; Metabolic Syndrome; Motor Activity; Tumor Necrosis Factor-alpha; Vegetables

The aim of this study was to determine whether the highest vitamin C supplementation associated with complete bioavailability influences the plasma and blood mononuclear cell IL-6 and IL-10 response to exercise. A double-blinded study of supplementation with vitamin C was performed. After 15 days of supplementation with vitamin C (500 mg · day(-1), n = 16) or a placebo (n = 15), participants in the study completed a 15-km run competition. Blood samples were taken before and after competition. Oxidative stress markers, antioxidants, cortisol, IL-6 and IL-10 were determined in plasma or serum. IL-6 and IL-10 protein and mRNA levels were measured in blood mononuclear cells. Although higher plasma and blood mononuclear cell vitamin C levels were observed in the supplemented group when compared with the placebo one, the two groups showed identical exercise-induced changes in all the measured parameters. Exercise induced increased IL-6 and IL-10 levels in plasma and blood mononuclear cells. IL-6 and IL-10 mRNA levels in blood mononuclear cells increased after the competition. After recovery, IL-6 mRNA returned to basal levels and IL-10 mRNA levels remained elevated. In conclusion, exercise induced increased IL-6 and IL-10 production in blood mononuclear cells. However, vitamin C supplementation did not influence IL-6 and IL-10 response to exercise.

Topics: Adult; Antioxidants; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Exercise; Humans; Hydrocortisone; Inflammation; Interleukin-10; Interleukin-6; Leukocytes, Mononuclear; Male; Oxidative Stress; RNA, Messenger; Running; Vitamins

Vitamin C has important physical and mental health benefits and plasma concentrations reflect recent intakes. Inflammation associated with any acute illness can lead to poor appetite and low food intake in older people. The aims of this report were to assess the prevalence and clinical significance of vitamin C deficiency among hospitalized acutely-ill older patients.. Three hundred and twenty two patients (152 [47%] female), aged 65 yrs. and over who took part in a randomized, double blind, placebo-controlled trial had their nutritional status assessed from anthropometric, hematological and biochemical data at baseline, and after 6 weeks and 6 months. Vitamin C was measured using a fluorimetric technique and logistic regression analysis was performed to determine the influence of a number of clinical indicators, including tissue inflammation measured using C-reactive protein on vitamin C concentrations. Clinical outcome measures including symptoms of depression were also compared between patients with vitamin C deficiency and those with normal levels.. At baseline, 116 (36%) patients had a vitamin C concentration below 11 µmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 28 (22%) and 44 (28%) patients, respectively. Older age, male gender, smoking, increased dependency and tissue inflammation were associated with lower vitamin C concentrations. Patients with vitamin C biochemical depletion had significantly increased symptoms of depression compared with those with higher concentrations at baseline (p=0.035) and at 6 weeks (p=0.028).. A high proportion of older patients had sub-optimal vitamin C status and this was associated with increased symptoms of depression.

Topics: Acute Disease; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Depression; Double-Blind Method; Female; Hospitalization; Humans; Inflammation; Male; Nutritional Status; Placebos; Prognosis; Sex Factors; Smoking

It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested.. 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured.. After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia.. This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Dinoprost; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inflammation; Inflammation Mediators; Infusions, Parenteral; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Oxidative Stress; Reperfusion Injury; Time Factors; Treatment Outcome; Tyrosine; Vasodilation; Young Adult

This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of post-operative atrial fibrillation.. Therapy to prevent post-operative atrial fibrillation remains suboptimal. Although oxidative stress plays a key role in the pathogenesis of this arrhythmia, antioxidant reinforcement has produced controversial results.. A total of 203 patients scheduled for on-pump cardiac surgery were randomized to placebo or supplementation with n-3 polyunsaturated fatty acids (2 g/day) (eicosapentaenoic acid:docosahexaenoic acid ratio 1:2), vitamin C (1 g/day), and vitamin E (400 IU/day). The primary outcome was the occurrence of post-operative atrial fibrillation. Secondary outcomes were the biomarkers related to oxidative stress and inflammation.. Post-operative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05).. This safe, well-tolerated, and low-cost regimen, consisting of n-3 polyunsaturated fatty acids plus vitamins C and E supplementation, favorably affected post-operative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation. (Prevention of Post-Operative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning; ISRCTN45347268).

Topics: Antioxidants; Ascorbic Acid; Atrial Fibrillation; Biomarkers; Cardiac Surgical Procedures; Dietary Supplements; Drug Monitoring; Fatty Acids, Omega-3; Female; Humans; Inflammation; Male; Middle Aged; Outcome Assessment, Health Care; Oxidative Stress; Postoperative Complications; Treatment Outcome; Vitamin E

To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1 diabetes.. A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.. This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.

Topics: Acute Disease; Antioxidants; Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelium, Vascular; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Inflammation; Infusions, Intravenous; Insulin; Male; Oxidative Stress; Vasodilation; Young Adult

Evidence has shown that both C-reactive protein (CRP) and serum amyloid component A (SAA) are increased in individuals with gastritis and stomach cancer. Controlling the level of these biomarkers by inhibiting the gastric infection with high doses of ascorbic acid may reduce the risk of carcinogenesis. A population-based double-blind randomised controlled trial in a Japanese population with atrophic gastritis in an area of high stomach cancer incidence was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were given, and 120 and 124 participants completed the 5-year study, respectively. Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46) μg/l) than in the low-dosage group (1.49 (SD 0.29) μg/l, P< 0.001), at the end of the study, no significant difference was observed for CRP between the low- and high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31) mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups (3.94 (95 % CI 1.04, 14.84) μg/ml and 3.85 (95 % CI 0.99, 14.92) μg/ml, respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on reducing infections in individuals with atrophic gastritis.

Topics: Adult; Aged; Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Double-Blind Method; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Japan; Male; Middle Aged; Serum Amyloid A Protein; Stomach Neoplasms

Erythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-β(0) -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.

Topics: Adolescent; Adult; Aged; Anemia, Sickle Cell; Antioxidants; Ascorbic Acid; Biomarkers; Dietary Supplements; Double-Blind Method; Drug Utilization; Female; Hemolysis; Hospitalization; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Quality of Life; Reactive Oxygen Species; Sickle Cell Trait; Thalassemia; Vitamin E; Young Adult

Two milk-based beverages delivering twice the average daily antioxidant intake were formulated, based on synergistic combinations of fruit and vegetable extracts, and containing vitamin C (1.00 mg/ml) for shelf stability. Smokers (n = 42) consumed prototype milk A, B or non-supplemented milk (no extracts or vitamin C; 200 ml) twice daily for 6 weeks. Fasting and post-prandial (2 h after milk consumption) blood samples were collected at baseline and the end of each treatment. Non-supplemented milk significantly reduced fasting inflammatory cytokines (interleukin (IL) 6, IL-1β, tumour necrosis factor-α) compared to baseline. Both supplemented milk-based beverages significantly increased fasting plasma vitamin C concentrations and antioxidant potential and decreased serum uric acid, compared to non-supplemented milk. The beverages did not induce post-prandial oxidative stress or inflammation. Therefore, regular consumption of the supplemented milks may confer health benefits because of increased antioxidant potential or through mechanisms resulting from increased vitamin C or decreased uric acid concentrations.

Topics: Adult; Animals; Antioxidants; Ascorbic Acid; Beverages; Biomarkers; Cross-Over Studies; Cytokines; Diet; Dietary Supplements; Double-Blind Method; Fasting; Female; Food, Fortified; Fruit; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Milk; Oxidative Stress; Plant Extracts; Postprandial Period; Smoking; Uric Acid; Vegetables

Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.

Topics: Aged; Analysis of Variance; Antioxidants; Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Extracorporeal Circulation; Fatty Acids, Omega-3; Female; Glutathione Disulfide; Humans; Inflammation; Lipid Peroxidation; Logistic Models; Male; Malondialdehyde; Middle Aged; NF-kappa B; Oxidative Stress; Protein Carbonylation; Thoracic Surgical Procedures; Vitamin E

The effect of ascorbic acid on inflammatory markers after cardiothoracic surgery (CTS) was studied.. In this randomized, double-blind, placebo-controlled trial, patients undergoing cardiopulmonary bypass graft surgery or valve replacement surgery from April 2009 through March 2010 at Hartford Hospital were randomized to receive ascorbic acid (2-g loading dose followed by 500 mg every 12 hours) or matching placebo the evening before surgery and for four days postoperatively. Inflammatory mediators were measured preoperatively and on postoperative days 1-4. Intergroup comparisons were performed using two-tailed t tests and Fisher's exact test. Multiple comparisons were conducted using repeated analyses of variance with Bonferroni tests.. Of the 62 patients screened, 24 met the study inclusion criteria. Of these, 13 were assigned to receive ascorbic acid and 11 received placebo. Ascorbic acid did not affect the natural course of inflammatory marker rise for C-reactive protein (CRP) concentration, white blood cell (WBC) count, or fibrinogen concentration versus placebo at any evaluated time point (p > 0.05 for all intergroup comparisons). Intragroup analyses demonstrated significant differences among baseline and postoperative measures of all inflammatory mediators (p < 0.05). No significant differences were noted in inflammatory markers between patients undergoing cardiothoracic surgery with or without cardiopulmonary bypass, regardless of treatment group.. Ascorbic acid did not attenuate the rise in inflammatory markers after CTS when compared with placebo. The use of off-pump surgery did not significantly change the levels of CRP and fibrinogen or the WBC count postoperatively when compared with on-pump surgery with a biocompatible polymer coating.

Topics: Aged; Ascorbic Acid; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Double-Blind Method; Female; Fibrinogen; Heart Valve Diseases; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Vitamins

Our goal was to explore whether antioxidant vitamin C infusion is able to affect the microcirculation perfusion in patients undergoing elective percutaneous coronary intervention for stable angina.. Periprocedural myocardial injury in the setting of elective percutaneous coronary intervention is associated with increased risk of death, recurrent infarction, and revascularization at follow-up. Despite excellent epicardial blood flow, impaired microcirculatory reperfusion may persist and increases the risk of vascular recurrences. Post-percutaneous coronary intervention induced-oxidative stress is one of the potential mechanisms accounting for impaired perfusion.. Fifty-six patients were enrolled in a prospective, single-center, randomized study comparing 1 g vitamin C infusion (16.6 mg/min, over 1 h before percutaneous coronary intervention) versus placebo.. At the baseline, Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade <2 was observed in 89% and in 86% of patients randomized to the placebo or vitamin C infusion group, respectively (p > 0.05). After percutaneous coronary intervention, these percentages decreased in the placebo group (32%) and in greater measure in the vitamin C group (4%, p < 0.01). Complete microcirculatory reperfusion (TIMI myocardial perfusion grade = 3) was achieved in 79% of the vitamin C-treated group compared with 39% of the placebo group (p < 0.01); 8-hydroxy-2-deoxyguanosine (p < 0.002) and 8-iso-prostaglandin F(2alpha) (p < 0.02) plasma levels significantly increased in the placebo group while they were significantly reduced in the vitamin C-treated group (p < 0.0001). TIMI myocardial perfusion grade changes from the baseline showed significant correlation with 8-hydroxy-2-deoxyguanosine (p < 0.006) or 8-iso-prostaglandin F(2alpha) (p < 0.01) plasma levels changes.. In patients undergoing elective percutaneous coronary intervention, impaired microcirculatory reperfusion is improved by vitamin C infusion suggesting that oxidative stress is implicated in such a phenomenon.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Biomarkers; Elective Surgical Procedures; Female; Health Status Indicators; Humans; Inflammation; Male; Microcirculation; Middle Aged; Multivariate Analysis; Myocardial Reperfusion; Oxidative Stress; Statistics as Topic; Stroke Volume; Ventricular Function, Left

The modern Western lifestyle is characterized by the consumption of high-heat-treated foods because of their characteristic taste and flavor. However, it has been shown that treating food at high temperatures can generate potentially harmful compounds that promote inflammation and cardiovascular disease in subjects with diabetes.. The aim of this study was to determine whether high-heat-treated foods also pose a risk for healthy subjects.. A randomized, crossover, diet-controlled intervention trial with 62 volunteers was designed to compare the potential metabolic effects of 2 diets, one that was based on mild steam cooking and another that was based on high-temperature cooking. These 2 diets differed mainly in their contents of Maillard reaction products (MRPs). MRPs were assessed in the diet and in subjects' feces, blood, and urine samples, with N(epsilon)-carboxymethyllysine as an indicator of MRPs. Biological indicators of glucose and lipid metabolism as well as oxidative stress were analyzed in subjects after 1 mo on each diet.. In comparison with the steamed diet, 1 mo of consuming the high-heat-treated diet induced significantly lower insulin sensitivity and plasma concentrations of long-chain n-3 (omega-3) fatty acids and vitamins C and E [-17% (P < 0.002), -13% (P < 0.0001), and -8% (P < 0.01), respectively]. However, concentrations of plasma cholesterol and triglycerides increased [+5% (P < 0.01) and +9% (P < 0.01), respectively].. A diet that is based on high-heat-treated foods increases markers associated with an enhanced risk of type 2 diabetes and cardiovascular diseases in healthy people. Replacing high-heat-treatment techniques by mild cooking techniques may help to positively modulate biomarkers associated with an increased risk of diabetes mellitus and cardiovascular diseases.

Topics: Ascorbic Acid; Body Mass Index; Cardiovascular Diseases; Cholesterol; Cooking; Cross-Over Studies; Diabetes Mellitus, Type 2; Fatty Acids, Omega-3; Female; Hot Temperature; Humans; Inflammation; Insulin; Life Style; Maillard Reaction; Male; Risk Factors; Triglycerides; Vitamin E; Young Adult

Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease, diabetes, and cancer. A high "inflammatory load" is defined as elevated inflammation markers in blood or other tissues. We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders (FVB) or without (FV) could impact markers of inflammatory load. Using a double-blind, placebo-controlled approach, 117 subjects were randomly assigned to receive placebo, FV, or FVB capsules. Blood was drawn at baseline and after 60 d of capsule consumption. We measured inflammatory markers (high sensitivity C-Reactive Protein, Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-β, and Regulated upon Activation, Normal T cell Expressed and Secreted), superoxide dismutase, and micronutrients (β-carotene, vitamin C, and vitamin E). Results showed Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-β, and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB, relative to placebo. Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; beta Carotene; Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Dietary Supplements; Double-Blind Method; Female; Fruit; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Superoxide Dismutase; Vegetables; Vitamin E; Young Adult

A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress.. Patients received an intra-operative intravenous infusion of 50 mg melatonin or placebo. In addition, all patients received 10 mg melatonin or placebo orally the first 3 nights after surgery. Blood samples for analysis of malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA) and C-reactive protein (CRP) were collected preoperatively, and at 5 min, 6 h and 24 h after clamp removal (recirculation of the first leg).. Twenty-six patients received melatonin and 24 patients received placebo. No significant differences were observed in any of the oxidative and inflammatory stress parameters. There were significantly more side effects in the melatonin group than in the placebo group.. Melatonin treatment in the perioperative period did not reduce the oxidative and inflammatory parameters measured in this study.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Ascorbic Acid; Biomarkers; C-Reactive Protein; Chi-Square Distribution; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Double-Blind Method; Female; Humans; Inflammation; Infusions, Intravenous; Male; Malondialdehyde; Melatonin; Middle Aged; Oxidative Stress; Placebos; Statistics, Nonparametric; Treatment Outcome; Vascular Surgical Procedures

Muscle atrophy commonly follows anterior cruciate ligament (ACL) injury and surgery. Proinflammatory cytokines can induce and exacerbate oxidative stress, potentiating muscle atrophy. The purpose of this study was to evaluate the influence of prior antioxidant (AO) supplementation on circulating cytokines following ACL surgery. A randomized, double-blind, placebo-controlled trial was conducted in men undergoing ACL surgery, who were randomly assigned to either: (1) AO (200 IU of vitamin E (50% d-alpha-tocopheryl acetate and 50% d-alpha-tocopherol) and 500 mg ascorbic acid), or (2) matching placebos (PL). Subjects took supplements twice daily for 2 weeks prior to and up to 12 weeks after surgery. Each subject provided five blood samples: (1) baseline (Bsl, prior to supplementation and approximately 2 weeks prior to surgery), (2) presurgery (Pre), (3) 90 min, (4) 72 h, and (5) 7 days postsurgery. Following surgery, inflammation and muscle damage increased in both groups, as assessed by increased circulating IL-6, C-reactive protein, and creatine kinase. During AO supplementation, plasma alpha-T and AA increased while gamma-T concentrations decreased significantly (P< 0.05). At 90 min the AO group displayed a significant decrease in AA, an inverse correlation between AA and (interleukin) IL-8 (r(2)= 0.50, P< 0.05), and a significantly lower IL-10 response than that of the PL group. IL-10 was significantly elevated at 90 min and 72 h in the PL group. In summary, our findings show that circulating inflammatory cytokines increase and AO supplementation attenuated the increase in IL-10 in patients post-ACL surgery.

Topics: Adult; alpha-Tocopherol; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Ascorbic Acid; C-Reactive Protein; Creatine Kinase; Cytokines; Dietary Supplements; Double-Blind Method; gamma-Tocopherol; Humans; Inflammation; Male; Muscular Atrophy, Spinal; Plastic Surgery Procedures

A human study was carried out to investigate whether tomato juice, rich in natural lycopene and fortified with vitamin C, is able to reduce several biomarkers of oxidative stress and inflammation and whether the effect can be attributed to lycopene, vitamin C or any other micronutrient. Following a 2-week depletion phase, volunteers were assigned randomly to ingest either tomato juice with (LC) or without (L) vitamin C fortification for 2 weeks (daily dose 20.6 mg lycopene and 45.5/435 mg vitamin C). Plasma and urine were analysed for carotenoids and vitamin C, lipid status, antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and 8-epi-PGF2alpha, protein carbonyls, cytokines IL-1beta and TNFalpha and C-reactive protein (CRP). The consumption of tomato juice led to a reduction in total cholesterol levels (L: 157.6 v. 153.2 mg/dl, P = 0.008; LC: 153.4 v. 147.4 mg/dl, P = 0.002) and that of CRP (L: 315.6 v. 262.3 microg/l, P = 0.017; LC: 319.2 v. 247.1 microg/l, P = 0.001) in both groups. The vitamin C-fortified juice slightly raised the antioxidant capacity in urine and decreased TBARS in plasma and urine. All other markers were affected to a lesser extent or remained unchanged. Cholesterol reduction was correlated with lycopene uptake (P = 0.003), whereas the other effects could not be related with particular micronutrients. Any beneficial effects of tomato consumption for human health cannot be attributed only to lycopene and, as the additional supplementation with ascorbic acid indicates, a variety of antioxidants might be needed to optimize protection against chronic diseases.

Topics: Adult; Analysis of Variance; Antioxidants; Ascorbic Acid; beta Carotene; Beverages; Biomarkers; C-Reactive Protein; Carotenoids; Cholesterol; Dietary Supplements; Female; Humans; Inflammation; Interleukin-1; Lycopene; Male; Oxidative Stress; Solanum lycopersicum; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

The objective of this study was to test the hypothesis that the inflammatory response to a high-fat, low-carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI>27 kg/m(2)) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre- and post serum samples were measured for markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8-epi-prostaglandin-F(2alpha) (8-epi)). HF resulted in significant reductions in weight (-3.2%), glucose (-18.7%), and MCP-1 (-15%) (all P<0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P=0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r= -0.501), 8-epi (r= -0.863), and ORAC (r= -0.546) (all P<0.05). It was concluded that weight loss on a short-term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet-controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Diet, Carbohydrate-Restricted; Dietary Fats; Dinoprost; Drug Combinations; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Obesity; Oxidative Stress; Reactive Oxygen Species; Time Factors; Treatment Outcome; Vitamin E; Weight Loss

It is unknown whether diets with a high dietary total antioxidant capacity (TAC) can modify oxidative stress, low-grade inflammation, or liver dysfunction, all of which are risk factors for type 2 diabetes and cardiovascular disease.. We studied the effect of high- and low-TAC (HT and LT, respectively) diets on markers of antioxidant status, systemic inflammation, and liver dysfunction.. In a crossover intervention, 33 healthy adults (19 men, 14 women) received the HT and LT diets for 2 wk each. Dietary habits were checked with a 3-d food record during both diet periods and the washout period.. Fruit and vegetable, macronutrient, dietary fiber, and alcohol intakes did not differ significantly between the 2 diets, whereas dietary TAC, alpha-tocopherol, and ascorbic acid were significantly (P < 0.001) higher during the HT diet. Plasma alpha-tocopherol rose during the HT and decreased during the LT diet (P < 0.02 for difference) without changes in markers of oxidative stress except plasma malondialdehyde, which decreased unexpectedly during the LT diet (P < 0.05). Plasma high-sensitivity C-reactive protein, alanine aminotransferase, gamma-glutamyltranspeptidase, and alkaline phosphatase concentrations decreased during the HT compared with the LT diet (mean +/- SEM for pre-post changes: -0.72 +/- 0.37 compared with 1.05 +/- 0.60 mg/L, P < 0.01; -1.73 +/- 1.02 compared with 2.33 +/- 2.58 U/L, P < 0.01; -2.12 +/- 1.45 compared with 5.15 +/- 2.98 U/L, P < 0.05; and 1.36 +/- 1.34 compared with 5.06 +/- 2.00 U/L, P < 0.01, respectively).. Selecting foods according to their TAC markedly affects antioxidant intake and modulates hepatic contribution to systemic inflammation without affecting traditional markers of antioxidant status.

Topics: Alanine Transaminase; Alkaline Phosphatase; alpha-Tocopherol; Antioxidants; Ascorbic Acid; C-Reactive Protein; Cross-Over Studies; Diet; Diet Records; Female; gamma-Glutamyltransferase; Humans; Inflammation; Liver; Male; Malondialdehyde; Middle Aged; Oxidation-Reduction; Oxidative Stress

Vitamin supplements have been reported to reduce the magnitude of symptoms in subjects exposed to oxidant air pollution. To confirm whether supplementation with vitamins C and E could reduce lung function decrements, airway inflammation, and epithelial injury in subjects sensitive to ozone, a double-blinded, crossover control study was performed. Fourteen ozone-responsive subjects were randomly exposed to both air and ozone (0.2 ppm for 2 h) after 7 days of either placebo treatment or supplementation with vitamin C (500 mg/day) and E (100 mg/day). Lung function was assessed pre- and immediately postexposure and blood samples were taken at set intervals. Inflammatory, tissue injury, and antioxidant responses were examined in lavage fluid obtained by bronchoscopy 6 h postexposure. Exposure to ozone resulted in significant (P < 0.01) decrements in FEV1 with no protection observed following vitamin supplementation (-8.5%) versus placebo (-7.3%) treatment. Similarly, ozone-induced neutrophilia were of a similar magnitude after both treatments (P < 0.05). This lack of protection was observed despite elevated plasma vitamin C (+60.1%) and vitamin E (+51.4%) concentrations following supplementation, and increased vitamin C concentrations in the airways after supplementation following ozone exposure. These data do not therefore support the contention that acute ozone-induced symptoms can be attenuated through the use of dietary antioxidants in well-nourished individuals.

Topics: Air Pollutants; Ascorbic Acid; Dietary Supplements; Female; Humans; Inflammation; Lung; Lung Diseases; Male; Ozone; Respiratory Function Tests; Vitamin E; Vitamins

During endurance exercise, oxygen consumption by the skeletal muscle can increase 100-200 times. We previously found that during an ultramarathon race (50 km, forest trail through hilly terrain) compared with a day of rest, vitamin E disappeared faster (as measured using 2H-labelled alpha-tocopherol) and lipid peroxidation increased. Therefore, we hypothesized that prior supplementation with antioxidants (vitamins E and C) would decrease oxidative stress during distance running and, therefore, decrease lipid peroxidation and inflammation, decrease DNA damage, decrease muscle damage and/or improve recovery. To test these hypotheses, we carried out a randomized, double-blind study in runners (n 11 females, 11 males) who were participants in an annual ultramarathon race. We found that supplementation with both vitamins E and C only prevented increases in lipid peroxidation, but had no apparent effect on DNA damage, inflammation or muscle damage. These results suggest that the mechanism of oxidative damage is operating independently of the inflammatory and muscle damage responses.

Topics: Ascorbic Acid; Cytokines; Dietary Supplements; DNA Damage; Double-Blind Method; F2-Isoprostanes; Female; Humans; Inflammation; Lipid Peroxidation; Male; Muscle Fatigue; Oxidation-Reduction; Physical Exertion; Running; Vitamin E

The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis.. sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation.. In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15-15 microg/min.dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 microg/min.dl) or nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100 microg/min.dl) or the antioxidant vitamin C (8 mg/min.dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations.. sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by L-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of L-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib.. In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.

Topics: Acetylcholine; Adult; Algorithms; Ascorbic Acid; Celecoxib; Cyclooxygenase 2; Endothelium, Vascular; Female; Forearm; Hashimoto Disease; Humans; Indomethacin; Inflammation; Male; Membrane Proteins; Middle Aged; Nitric Oxide; Nitroprusside; Oxidative Stress; Pyrazoles; Regional Blood Flow; Sulfonamides; Vascular Diseases; Vasculitis; Vasodilation

Homocystinemia is a metabolic abnormality associated with endothelial dysfunction and increased cardiovascular disease risk. The underlying mechanisms of these effects, however, are obscure.. We examined the effect of asymmetrical dimethylarginine (ADMA) on endothelial dysfunction in methionine-induced and chronic homocystinemia and evaluated the regulatory role of oxidative stress and proinflammatory cytokines on the release of ADMA.. In this double-blind, placebo-controlled parallel group study, 30 subjects of both sexes (15 with homocystinemia and 15 healthy controls) underwent methionine loading, with simultaneous administration of a combination of vitamin C (2 g) plus alpha-tocopherol (800 IU) or placebo. Endothelial function in forearm resistance vessels and concentrations of ADMA, oxidized LDL, and proinflammatory cytokines were determined at baseline and 4 h after methionine loading.. Both chronic and methionine-induced homocystinemia were associated with increased oxidized LDL (P < 0.01), higher expression of the proinflammatory cytokine interleukin 6 (P < 0.05), and endothelial dysfunction (P < 0.01). Although ADMA rapidly increased in acute homocystinemia (P < 0.01) and was correlated with forearm hyperemic response at 4 h after methionine loading (r = -0.722, P = 0.0001), it was not higher in subjects with high versus low fasting homocysteine. High-dose antioxidant treatment prevented methionine-induced elevation of oxidized LDL and interleukin 6 but failed to prevent the increase in ADMA or endothelial dysfunction.. Both chronic and methionine-induced homocystinemia are characterized by increased oxidative stress and proinflammatory cytokines, which may contribute to the development of endothelial dysfunction. However, the ADMA pathway is activated only in acute homocystinemia by mechanisms not mediated by oxidized LDL or proinflammatory stimuli.

Topics: Adult; alpha-Tocopherol; Arginine; Ascorbic Acid; Cholesterol, LDL; Chronic Disease; Cytokines; Double-Blind Method; Endothelium, Vascular; Female; Forearm; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-6; Male; Methionine; Oxidative Stress; Time Factors; Vascular Resistance; von Willebrand Factor

To determine the influence of vitamin C supplementation (500 mg, bd, 14 days) on the circulating concentrations of soluble ICAM-1 (a marker of endothelial activation), neopterin (a marker of monocyte activation), and neutrophil elastase (a marker of neutrophil activation) in smokers and non-smokers in a randomised, double-blind, placebo-controlled trial in a hospital setting.. Twenty smokers (serum cotinine > or = 20 ng ml(-1)) and 20 age- and gender-matched non-smokers (serum cotinine < or = 13.7 ng ml(-1)).. At baseline, there was a significant elevation in the concentration of sICAM-1 in smokers (median 247, IQR 199 to 357 ng ml(-1)) compared to non-smokers (median 207, IQR 189 to 227 ng ml(-1); p = 0.014). Vitamin C supplementation did not influence the circulating concentrations of ICAM-1 or neopterin, or leukocyte elastase activity, in smokers, non-smokers, or in the total population.. Markers of monocyte and neutrophil activation were not influenced by smoking status in this study population. However, sICAM-1 concentrations were significantly elevated in tobacco smokers, reflecting tobacco-induced vascular activation that is unaffected by Vitamin C supplementation.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Cotinine; Endothelium; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukocyte Elastase; Lung; Male; Middle Aged; Neopterin; Placebos; Smoking; Time Factors

There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients. Limited data, however, are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients.. We ran a prospective, randomized, open-label trial to assess the effects of oral vitamin C supplementation (250 mg three times per week) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis (HD) patients.. Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls, C-reactive protein and albumin, or erythrocyte concentrations of reduced and oxidized glutathione.. Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients. Whether a higher oral dose or the intravenous route can modify these markers remains to be determined.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Smoking

Inflammation and oxidative stress have been recently implicated in the pathophysiology of atrial fibrillation (AF). The aim of this study was to examine the potential benefit of vitamin C on the early recurrence rates and on inflammatory indices after successful cardioversion of persistent AF, as well as to investigate the time course of changes in these indices post-cardioversion.. We prospectively studied 44 consecutive patients after successful electrical cardioversion of persistent AF. All patients received standard treatment and were randomised in one to one fashion to either oral vitamin C administration or no additional therapy. We followed-up the patients for 7 days performing successive measurements of white blood cell (WBC) count, C-reactive protein (CRP), fibrinogen, and ferritin levels.. One week after successful cardioversion, AF recurred in 4.5% of patients in the vitamin C group and in 36.3% of patients in the control group (p=0.024). Compared to baseline values, inflammatory indices decreased after cardioversion in patients receiving vitamin C but did not change significantly in the control group. A significant variance was found in the serial measurements of WBC counts (F=5.86, p=0.001) and of fibrinogen levels (F=4.10, p=0.0084) in the two groups. In the vitamin C group CRP levels were lower on the seventh day (p<0.05). CRP and fibrinogen levels were higher in patients who relapsed into AF compared to patients who maintained sinus rhythm (F=2.77, p=0.044 and F=3.51, p=0.017, respectively).. These findings suggest that vitamin C reduces the early recurrence rates after cardioversion of persistent AF and attenuates the associated low-level inflammation. These effects indicate that therapeutic approaches targeting at inflammation and oxidative stress may exert favourable effects on atrial electrical remodeling.

Topics: Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Echocardiography; Electric Countershock; Electrocardiography; Female; Ferritins; Fibrinogen; Follow-Up Studies; Heart Atria; Humans; Incidence; Inflammation; Leukocyte Count; Male; Myocarditis; Nephelometry and Turbidimetry; Oxidative Stress; Prospective Studies; Secondary Prevention; Treatment Outcome

An inflammatory component has been identified in degenerative aortic stenosis (AS). The combination of vitamins E and C has been shown to have anti-inflammatory properties. The aim of this study was to determine the impact of the combination of vitamins C and E or vitamin C only on serum levels of cell adhesion molecules and C-reactive protein in patients with chronic degenerative AS, with or without concomitant coronary artery disease.. One hundred patients with asymptomatic or mildly symptomatic moderate AS were randomized in 2:2:1 format in an open-label trial. Forty-one patients received vitamin E (400 IU) and vitamin C (1000 mg) daily, 39 patients received vitamin C (1000 mg) only, and 20 patients were followed as controls. Serum intracellular adhesion molecule (ICAM-1), E selectin, P selectin, vascular-cellular adhesion molecule (VCAM-1), C-reactive protein, and alpha-tocopherol (vitamin E) were measured by enzyme-linked immunosorbent assay at baseline and 6 months postsupplementation. Half of the patients from each of the 2 active groups were followed for further 6 months to determine any changes after cessation of therapy. In the vitamin E and C, group there was reduction in serum ICAM-1 (298 +/- 12 to 272 +/- 12 ng/mL at 6 months, P = .0015) with a return to base line 6 months after cessation of therapy. In the vitamin C only group, there was a reduction in serum P selectin (134 +/- 10 to 118 +/- 10 ng/mL at 6 months, P = .033). All the inflammatory markers were unchanged in control group over 6 months of follow-up.. Vitamin E and C supplementation had modest anti-inflammatory effect in chronic degenerative AS. The clinical relevance of this would require further clarification.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aortic Valve Stenosis; Ascorbic Acid; C-Reactive Protein; Cell Adhesion Molecules; Drug Therapy, Combination; E-Selectin; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Male; Middle Aged; P-Selectin; Treatment Outcome; Vascular Cell Adhesion Molecule-1; Vitamin E

Parenteral nutrition, a commonly used procedure in patients with gastrointestinal disorders, may lead with time to liver steatosis and fibrosis, whose pathogenesis has yet to be elucidated. Oxidative stress and particularly lipid peroxidation likely contribute to the expression of such hepatobiliary complications, by means of their recognized proinflammatory and profibrogenic effects. To evaluate the adequacy against oxidative insult of a standard micronutrient supplementation in patients under long term parenteral nutrition, a comprehensive patterns of redox indices has been determined on peripheral blood samples from forty one adults in comparison to fifty eight blood donors taken as controls. A sustained oxidative stress in peripheral blood of home parenteral patients was observed. Of the two lipid peroxidation markers found to be markedly increased, namely fluorescent plasma protein adducts with malondialdehyde and 4-hydroxynonenal, respectively, only the second was statistically correlated with all the antioxidant-related changes consistently detected in the patients, namely decreased plasma alpha-tocopherol and selenium intake and higher erythrocyte oxidized glutathione. Plasma level of 4-hydroxynonenal-protein adducts appears to be a reliable and easily measurable marker of oxidative status, particularly indicated to monitor the adequacy of dietary regimen during parenteral nutrition.

Topics: Adult; Aged; Aldehydes; alpha-Tocopherol; Ascorbic Acid; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Humans; Inflammation; Kidney Function Tests; Lipid Peroxidation; Liver Function Tests; Male; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Parenteral Nutrition, Home; Predictive Value of Tests; Proteins; Reference Values; Selenium; Vitamin A

To determine if 6 weeks of supplementation with vitamins E and C could alleviate exercise-induced lipid peroxidation and inflammation, we studied 22 runners during a 50 km ultramarathon. Subjects were randomly assigned to one of two groups: (1) placebos (PL) or (2) antioxidants (AO: 1000 mg vitamin C and 300 mg RRR-alpha-tocopheryl acetate). Blood samples were obtained prior to supplementation (baseline), after 3 weeks of supplementation, 1 h pre-, mid-, and postrace, 2 h postrace and for 6 days postrace. Plasma levels of alpha-tocopherol (alpha-TOH), ascorbic acid (AA), uric acid (UA), F2-isoprostanes (F2-IsoPs), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured. With supplementation, plasma alpha-TOH and AA increased in the AO but not the PL group. Although F2-IsoP levels were similar between groups at baseline, 28 +/- 2 (PL) and 27 +/- 3 pg/ml (AO), F2-IsoPs increased during the run only in the PL group (41 +/- 3 pg/ml). In PL women, F2-IsoPs were elevated postrace (p <.01), but returned to prerace concentrations by 2 h postrace. In PL men, F2-IsoP concentrations were higher postrace, 2 h postrace, and 1, 2, 3, 4, and 6 days postrace (PL vs. AO group, each p <.03). Markers of inflammation were increased dramatically in response to the run regardless of treatment group. Thus, AO supplementation prevented endurance exercise-induced lipid peroxidation but had no effect on inflammatory markers.

Topics: Adolescent; Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Exercise; F2-Isoprostanes; Female; Humans; Inflammation; Interleukin-6; Lipid Peroxidation; Male; Middle Aged; Running; Tumor Necrosis Factor-alpha; Uric Acid; Vitamin E

Acute inflammation causes endothelial vasodilator dysfunction that may be mediated by oxidative stress.. In this randomized, double-blind, crossover study, forearm blood flow responses to acetylcholine (ACh) (endothelium-dependent dilator) and glyceryl-trinitrate (GTN) (endothelium-independent dilator) were assessed before and after induction of acute systemic inflammation by low doses of Escherichia coli endotoxin (LPS) (20 IU/kg IV) in 8 healthy volunteers. The acute effect of intra-arterial vitamin C (24 mg/min) or placebo was studied 4 hours after LPS, respectively. Vitamin C alone was administered in control experiments. LPS administration caused systemic vasodilation, increased white blood count, elevated body temperature, and reduced vitamin C plasma concentrations. LPS decreased the responses of forearm blood flow to ACh by 30% (P<0.05) but not to GTN. Vitamin C completely restored the response to ACh, which was comparable with that observed under baseline conditions. Vitamin C had no effect on basal blood flow or ACh- or GTN-induced vasodilation in control subjects.. Our data demonstrate that impaired endothelial vasodilation caused by E coli endotoxemia can be counteracted by high doses of antioxidants in vivo. Oxidative stress may play an important role in the pathogenesis of endothelial dysfunction during inflammation.

Topics: Acetylcholine; Adult; Antioxidants; Ascorbic Acid; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Escherichia coli; Forearm; Humans; Inflammation; Lipopolysaccharides; Male; Nitroglycerin; Oxidative Stress; Plethysmography; Regional Blood Flow; Vasodilation; Vasodilator Agents

To test whether vitamin C and E supplements to triple therapy can improve the Helicobacter pylori eradication rate and gastric inflammation.. A total of 104 H. pylori-infected patients were randomized to receive: either lansoprazole, amoxicillin, and metronidazole twice daily for 1 week (triple-only group) or lansoprazole, amoxicillin, metronidazole plus vitamin C (250 mg) and vitamin E (200 mg) twice daily for 1 week, followed immediately by vitamin C and E once daily for 6 consecutive weeks (triple-plus-vitamin group). Eight weeks after the completion of triple therapy, patients were assessed for the effectiveness of H. pylori eradication. The severity of gastric inflammation in histology was assessed for the acute and chronic inflammation scores.. Intention-to-treat and per-protocol eradication rates were 59.1% and 64.4% in the triple-only group, and 40% and 44% in the triple-plus-vitamin group. In the patients infected with metronidazole susceptible isolates, the triple-only group had a higher intention-to-treat eradication rate than those in the triple-plus-vitamin group (80% vs. 53.1%, p <.01). However, for the metronidazole resistance isolates, the intention-to-treat eradication rates between the two groups were not different (26.3% vs. 21.7%, p = NS). The improvements of both acute and chronic inflammation scores in histology were not different between the two groups.. Adding vitamin C and E to triple therapy cannot improve the H. pylori eradication rate and gastric inflammation. For patients with metronidazole susceptible strain infection, adding these vitamins may even reduce the eradication rate of triple therapy.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Amoxicillin; Anti-Bacterial Agents; Ascorbic Acid; Dietary Supplements; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Lansoprazole; Male; Metronidazole; Omeprazole; Severity of Illness Index; Stomach Diseases; Treatment Outcome; Vitamin E

In this clinical trial we studied whether oral supplementation with D-alpha-tocopherol (alpha-Toc), L-ascorbic acid (Asc), or alpha-Toc combined with Asc influenced the solar simulated radiation (SSR) induced skin inflammation in healthy volunteers.. We investigated the following groups in a prospective, randomized and placebo controlled study: Group (1) alpha-Toc 2 g/day, group (2) Asc 3 g/day, group (3) alpha-Toc 2 g/day combined with Asc 3 g/day, and group (4) placebo. Before and 50 days after supplementation we analyzed alpha-Toc and Asc concentrations in keratinocytes. The dose response curve of UV erythema was determined by reflectance spectrophotometry and the minimal erythema dose (MED) by visual grading before and after supplementation.. 50 days after supplementation alpha-Toc keratinocyte levels were increased in groups (1) and (3), Asc concentrations were elevated in groups (2) and (3), and the a/gamma-Toc ratio increased in groups (1) and (3). The dose response curve of UVR induced erythema showed a significant flattening and the MED increased from 103 +/- 29 mJ/cm2 (before supplementation) to 183 +/- 35 mJ/cm2 (after supplementation) in group (3), while there were no significant changes in groups (1) and (2) after vitamin supplementation.. Alpha-Toc and Asc act synergistically in suppression of the sunburn reaction.

Topics: Administration, Oral; Antioxidants; Ascorbic Acid; Dietary Supplements; Drug Synergism; Erythema; Humans; Inflammation; Keratinocytes; Skin; Spectrophotometry; Sunburn; Ultraviolet Rays; Vitamin E

Several metabolic changes characteristic of the acute-phase response were examined in healthy men and women following a single 1 g dose of ascorbic acid. Utilizing a placebo-controlled, double-blind protocol, oral body temperatures were recorded in rested, fasted subjects (0900 hr) prior to the consumption of 1 g L-ascorbic acid or placebo (n = 10/group). Temperatures were recorded hourly for the next 8 hours, and again the next morning in the rested, fasted state (0900 hr). Blood samples, collected at 0, 4, and 24 hours post-dose, were analyzed for plasma ascorbate, iron, and zinc. Mean oral body temperature was significantly elevated 2 hours post-dose in the experimental subjects compared to controls (+0.7 degrees F, p = 0.03). In the vitamin-dosed subjects, mean plasma ascorbate rose 32% over the control value after 4 hours (1.11 +/- 0.08 and 0.84 +/- 0.06 mg/100 ml, ns). Serum iron levels were similar in the two groups at 0 and 4 hours post-dose, but at 24 hours post-dose mean serum iron of the vitamin-dosed subjects fell to 73% of that recorded for the control subjects (77 +/- 8 and 105 +/- 10 micrograms/100 ml, p = 0.04). Plasma zinc levels were similar for both groups at 0, 4, and 24 hours post-dose. These data indicate that ascorbate administration, at a level commonly supplemented in the US diet, elicits several host metabolic responses similar to those observed following exposure to infectious or inflammatory agents. These metabolic changes are most likely due to the reducing potential of the vitamin and may factor in the reported prophylactic success of vitamin C supplementation.

Topics: Acute-Phase Reaction; Adolescent; Adult; Ascorbic Acid; Body Temperature; Clinical Trials as Topic; Double-Blind Method; Female; Fever; Humans; Inflammation; Iron; Male; Trace Elements; Zinc

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Topics: Arthritis, Rheumatoid; Ascorbic Acid; Ascorbic Acid Deficiency; Autism Spectrum Disorder; Child; Humans; Inflammation; Interleukin-17; Interleukin-23; Interleukin-6; Male; Scurvy

Renal failure caused by gentamicin is mainly mediated through oxidative damage, inflammation, and apoptosis. Hence, vitamin C and selenium, which have antioxidant, anti-inflammatory, and anti-apoptotic properties, and their nanoparticle forms, which have recently received attention, may reduce gentamicin-induced side effects. Therefore, the aim of this study was to investigate the therapeutic effects of vitamin C and selenium, and their nanoparticles on gentamicin-induced renal damage in male rats. 128 adult male Wistar rats were randomly divided into equal sixteen controlled and treated groups. Serum levels of uric acid, blood urea nitrogen, urea, and creatinine were measured. Renal levels of oxidative parameters such as MDA, SOD, and CAT and inflammatory parameters including IL-1β, and TNF-α were measured. Renal expression of Nrf2, NF-κB, Bcl-2, caspase-3, BAX and mTORc1 was also evaluated. The results showed that gentamicin causes oxidative damage, inflammation, apoptosis and disruption of autophagy in kidney tissue in a dose-dependent manner. However, treatment with vitamin C, selenium and their nanoparticles could significantly improve these effects. Also, the results showed that the inflammatory and oxidative parameters and the expression of genes involved in them and apoptosis in the gentamicin groups treated with vitamin C nanoparticles and selenium nanoparticles reduced significantly compared to those treated with vitamin C and selenium. It can be concluded that vitamin C, selenium and their nanoparticles can improve gentamicin-induced kidney damage by inhibiting oxidative damage, inflammation and apoptosis-induced by autophagy, and can be a good option for kidney damage caused by gentamicin or as an adjunctive treatment to reduce its side effects.

Topics: Animals; Antioxidants; Ascorbic Acid; Gentamicins; Inflammation; Kidney; Male; Oxidative Stress; Rats; Rats, Wistar; Renal Insufficiency; Selenium

Diabetic retinopathy (DR) is a common complication of diabetes with nocuous effects on patients' eye health, typically accompanies by excessive inflammation and oxidative stress. Insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) was engaged with inflammation, whereas its precise role in the DR process was unclear. And enhanced lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and decreased ascorbic acid (AA) were also found in DR. This study was to explore the regulatory role and mechanism of IGF2BP3, MALAT1 and AA in the high glucose (HG)-induced retinal pigment epithelial (RPE) cell injury.. ARPE-19 cells were treated with HG to establish the in vitro RPE cell injury model. The mRNA and protein levels of the gene were evaluated by qRT-PCR or Western blot. Immunofluorescence detected the translocation condition of the p65 protein. Inflammatory factor levels were detected by ELISA assays. Apoptosis was detected by flow cytometry. The binding interaction of IGF2BP3 and MALAT1 was validated by RIP-qPCR assays.. In HG-induced RPE cell injury, IGF2BP3 expression, inflammatory response and apoptosis were enhanced. Next, the IGF2BP3 activated the NF-κB signalling to promote the RPE cell injury development. MALAT1 could directly bind with IGF2BP3 and up-regulate its expression. In addition, AA ameliorated the HG-induced RPE cell injury through the regulation of MALAT1.. Ascorbic acid ameliorated HG-induced RPE cell injury by repressing the NF-κB signalling pathway via modulating the MALAT1/IGF2BP3 axis.

Topics: Ascorbic Acid; Cell Line; Diabetic Retinopathy; Epithelial Cells; Glucose; Humans; Inflammation; NF-kappa B; Retinal Pigments; RNA, Long Noncoding; Signal Transduction

Vitamin C remains an important, yet frequently unassessed, component of a healthy immune system though it may prove useful in alleviating the chronic inflammatory processes underlying chronic diseases such as coronary artery disease (CAD). Recent research identified a sizeable proportion of the United States population with insufficient vitamin C plasma levels and significant associations to both acute and chronic inflammation. This cross-sectional study used the 2003-2006 NHANES surveys data to extrapolate associations between plasma vitamin C levels (deficiency, hypovitaminosis, inadequate, adequate, and saturating) and CAD through inflammation (C-reactive protein and red cell distribution width). Increased reports of CAD diagnosis were identified in participants with vitamin C deficiency (OR: 2.31, CI: 1.49-3.58) and inadequate plasma levels (OR: 1.39, CI: 1.03-1.87). No significant correlation was identified between any other plasma vitamin C quintiles and CAD. When inflammation was controlled, previous associations in the deficient level of plasma vitamin C were no longer significant in association with CAD and participants with inadequate plasma vitamin C showed a reduced association to CAD diagnoses (OR: 0.33, CI: 0.13-0.86). Most chronic inflammation and vitamin C plasma statuses do not demonstrate specific signs or symptoms until the deficient level of vitamin C and/or disease. Thus, increased surveillance of both, and healthy nutritional habits remain crucial modifiable risk factors for disease prevention.

Topics: Ascorbic Acid; Coronary Artery Disease; Cross-Sectional Studies; Humans; Inflammation; Nutrition Surveys; Risk Factors; Vitamins

Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Atrazine; Biomarkers; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Humans; Immunomodulation; Inflammation; Liver; Nanoparticles; Oxidative Stress; Rats; Reactive Oxygen Species; Vitamins; Zinc Oxide

Ascorbic acid has been suggested to regulate obesity in obese male rodents. Moreover, increased adipocyte size has been associated with metabolic disease. Thus, we investigated the effects of ascorbic acid on adipocyte hypertrophy and insulin resistance in high-fat diet (HFD)-induced obese ovariectomized (OVX) C57BL/6J mice, an animal model of obese postmenopausal women. Administration of ascorbic acid (5% w/w in diet for 18 weeks) reduced the size of visceral adipocytes without changes in body weight and adipose tissue mass in HFD-fed obese OVX mice compared with obese OVX mice that did not receive ascorbic acid. Ascorbic acid inhibited adipose tissue inflammation, as shown by the decreased number of crown-like structures and CD68-positive macrophages in visceral adipose tissues. Ascorbic acid-treated mice exhibited improved hyperglycemia, hyperinsulinemia, and glucose and insulin tolerance compared with nontreated obese mice. Pancreatic islet size and insulin-positive β-cell area in ascorbic acid-treated obese OVX mice decreased to the levels observed in low-fat diet-fed lean mice. Ascorbic acid also suppressed pancreatic triglyceride accumulation in obese mice. These results suggest that ascorbic acid may reduce insulin resistance and pancreatic steatosis partly by suppressing visceral adipocyte hypertrophy and adipose tissue inflammation in obese OVX mice.

Topics: Adipocytes; Animals; Ascorbic Acid; Diet, High-Fat; Female; Hypertrophy; Inflammation; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Pancreatic Diseases

The herbicide "Roundup" is used extensively in agriculture to control weeds. However, by translocation, it can be deposited in plants, their proceeds, and the soil, thus provoking organ toxicities in exposed individuals. Neurotoxicity among others is one of the side effects of roundup which has led to an increasing global concern about the contamination of food by herbicides. Xylopia aethiopica is known to have medicinal properties due to its antioxidative and anti-inflammatory properties, and it is hypothesized to neutralize roundup-induced neurotoxicity. Thirty-six (36) Wistar rats were used for this study. The animals were shared equally into six groups with six rats each. Glyphosate administration to three of the six groups was done orally and for 1 week. Either Xylopia aethiopica or vitamin C was co-administered to two of the three groups and also administered to two other groups and the final group served as the control. Our studies demonstrated that glyphosate administration led to a significant decrease in antioxidants such as catalase, superoxide dismutase, glutathione, and glutathione peroxidase. We also observed a significant increase in inflammatory markers such as tumor necrosis factor-α, interleukin 6, C-reactive protein, and immunohistochemical expression of caspase-3, cox-2, and p53 proteins (p < 0.05). However, Xylopia aethiopica co-administration with glyphosate was able to ameliorate the aforementioned changes when compared to the control (p < 0.05). Degenerative changes were also observed in the cerebellum, hippocampus, and cerebral cortex upon glyphosate administration. These changes were not observed in the groups treated with Xylopia aethiopica and vitamin C. Taken together, Xylopia aethiopica could possess anti-oxidative and anti-inflammatory properties that could be used in combating glyphosate neurotoxicity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Brain; Cell Death; Glyphosate; Herbicides; Inflammation; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Xylopia

Ascorbic acid has many benefits to the skin. Numerous attempts to promote its topical delivery show great challenges since its chemical instability and poor skin impermeability. Microneedle delivery is a simple, safe, painless and effective means to deliver therapeutic or nourishing molecules into the skin. The purpose of this study was twofold: (a) to develop a new formulation of ascorbic acid-loaded microneedles to enhance ascorbic acid stability by investigating an optimal amount of polyethyleneimine as an additive to the dextran-based microneedle formulation and (b) to assess microneedle properties in terms of dissolving rate, skin penetration ability, biocompatibility and antimicrobial activity.. The microneedles formulated with ascorbic acid and varied polyethyleneimine concentrations were fabricated and subsequently tested for ascorbic acid stability using 2,2-diphenyl-1-picrylhydrazyl assay. The dissolution rate and skin penetration depth were investigated in porcine skin and the reconstructed human full-thickness skin model respectively. The skin irritation tests were done according to the Organisation for Economic Co-operation and Development Test Guideline No. 439. An antimicrobial disc susceptibility test was performed against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.. Among varied amounts of 0%, 1.5%, 3.0% and 4.5% (w/v), the 3.0% polyethyleneimine showed the most desirable characteristics, including well-preserved shape integrity after demoulding, significantly improved stability of ascorbic acid (p < 0.001) from 33% to 96% antioxidant activity after 8 weeks of storage at 40°C, increased dissolving rate (p < 0.001) by being completely dissolved within 2 min after the skin insertion, passing skin penetration and biocompatibility tests as well as having a broad spectrum of antimicrobial property.. With a safety profile and enhanced properties, the new formulation of ascorbic acid-loaded microneedles shows outstanding potential as commercially available cosmetics and healthcare products.. L'acide ascorbique présente de nombreux avantages pour la peau. De nombreuses tentatives pour promouvoir sa délivrance topique présentent de grands défis en raison de son instabilité chimique et de sa faible imperméabilité cutanée. L'administration de micro-aiguilles est un moyen simple, sûr, indolore et efficace d'administrer des molécules thérapeutiques ou nourrissantes dans la peau. Le but de cette étude était double : a) développer une nouvelle formulation de microaiguilles chargées d'acide ascorbique pour améliorer la stabilité de l'acide ascorbique en étudiant une quantité optimale de polyéthylèneimine comme additif à la formulation de microaiguilles à base de dextrane ; et b) évaluer les propriétés des micro-aiguilles en termes de vitesse de dissolution, de capacité de pénétration cutanée, de biocompatibilité et d'activité antimicrobienne. MÉTHODES: Les microaiguilles formulées avec de l'acide ascorbique et des concentrations variées de polyéthylèneimine ont été fabriquées et ensuite testées pour la stabilité de l'acide ascorbique à l'aide d'un dosage de 2,2-diphényl-1-picrylhydrazyle. Le taux de dissolution et la profondeur de pénétration de la peau ont été étudiés dans la peau de porc et le modèle de peau humaine reconstruite de pleine épaisseur, respectivement. Les tests d'irritation cutanée ont été effectués conformément à la ligne directrice n° 439 de l'Organisation de coopération et de développement économiques. Un test de sensibilité du disque antimicrobien a été réalisé contre Escherichia coli, Staphylococcus aureus et Staphylococcusepidermidis. RÉSULTATS: Parmi des quantités variées de 0, 1,5, 3,0 et 4,5 % (p/v), la polyéthylèneimine à 3,0 % a montré les caractéristiques les plus souhaitables, notamment une intégrité de forme bien préservée après démoulage, une stabilité significativement améliorée de l'acide ascorbique (p ⟨ 0,001) de 33 % à 96 % d'activité antioxydante après 8 semaines de stockage à 40 °C, augmentation du taux de dissolution (p ⟨ 0,001) en étant complètement dissous dans les2 minutes suivant l'insertion de la peau, en passant les tests de pénétration cutanée et de biocompatibilité, ainsi qu'en ayant un large spectre de propriétés antimicrobiennes.. Avec un profil d'innocuité et des propriétés améliorées, la nouvelle formulation de micro-aiguilles chargées d'acide ascorbique présente un potentiel exceptionnel en tant que produits cosmétiques et de soins de santé disponibles dans le commerce.

Topics: Administration, Cutaneous; Animals; Anti-Infective Agents; Ascorbic Acid; Drug Delivery Systems; Humans; Inflammation; Needles; Polyethyleneimine; Skin; Swine

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Ghee; Inflammation; Liver; Male; Olive Oil; Plant Oils; Rabbits; Soybean Oil; Vitamin A; Vitamin E; Vitamin K; Vitamins

This study investigated the synergistic protective effects of melatonin (MEL) and ascorbic acid (vitamin C, ASA) in treating sepsis-induced lung injury in rats. Rats were divided into five groups: control, cecal ligation and puncture (CLP), CLP + MEL, CLP + ASA and CLP + MEL + ASA. The effects of MEL (10 mg/kg), ASA (100 mg/kg) and their combination on oxidative stress, inflammation and histopathology were evaluated in septic rats' lung tissues. Sepsis-induced oxidative stress and inflammation were evident through increased levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS) and oxidative stress index (OSI); decreased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx); and elevated levels of tumour necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in the lung tissue. Treatment with MEL, ASA and their combination significantly improved antioxidant capacity and reduced oxidative stress, with the combination treatment being more effective. The combination treatment also significantly reduced TNF-α and IL-1β levels and improved peroxisome proliferator-activated receptor (PPAR), arylesterase (ARE) and paraoxonase (PON) levels in the lung tissue. Histopathological examination showed reduced oedema and lymphocyte infiltration with a lung tissue appearance similar to the control group. Immunohistochemical staining for caspase 3 demonstrated reduced immune positivity in the treatment groups. In conclusion, this study supports the potential synergistic protective effects of MEL and ASA in treating sepsis-induced lung injury. The combination therapy could effectively reduce oxidative stress, inflammation and improve antioxidant capacity in septic rats, suggesting a promising strategy for treating sepsis-induced lung injury.

Topics: Animals; Antioxidants; Ascorbic Acid; Glutathione; Inflammation; Lung; Lung Injury; Melatonin; Oxidative Stress; Rats; Sepsis; Tumor Necrosis Factor-alpha

To investigate the combined therapeutic potential of melatonin and ascorbic acid in mitigating sepsis-induced heart and kidney injury in male rats and assess the combination therapy's effects on inflammation, cellular damage, oxidative stress, and vascular function-related markers.. Cecal ligation and puncture (CLP) induced sepsis in male rats, which were divided into five groups: Sham, CLP, MEL (melatonin), ASA (ascorbic acid), and MEL+ASA (melatonin and ascorbic acid). Rats were treated, and heart and kidney tissues were collected for biochemical and histopathological analyses. Inflammatory markers (presepsin, procalcitonin, NF-κB, IL-1β, IL-6, TNF-α), cellular damage marker (8-OHDG), oxidative status, nitric oxide (NO), vascular endothelial growth factor (VEGF), and sirtuin 1 (SIRT1) levels were assessed.. Melatonin and ascorbic acid treatment reduced inflammatory and cellular damage markers compared to the CLP group. Combined treatment improved NO, VEGF levels, and increased SIRT1 expression, suggesting a synergistic effect in mitigating sepsis-induced inflammation, cellular damage, and oxidative stress. Histopathological analyses supported these findings, revealing reduced heart and kidney injury in the MEL+ASA group.. Our study highlights potential benefits of combining melatonin and ascorbic acid as a therapeutic strategy for alleviating sepsis-induced heart and kidney injury. The synergistic effects of these agents may provide stronger protection against inflammation, oxidative stress, and tissue damage, opening new avenues for future research and clinical applications in sepsis management.

Topics: Animals; Ascorbic Acid; Inflammation; Kidney; Male; Melatonin; Rats; Rats, Sprague-Dawley; Sepsis; Sirtuin 1; Vascular Endothelial Growth Factor A

Topics: Antioxidants; Ascorbic Acid; Epigenesis, Genetic; Epithelial Cells; Humans; Inflammation; Iron; Lipid Peroxidation

The aim of this study was to demonstrate that swimming exercise combined with silymarin and vitamin C supplementation improves hepatic inflammation, oxidative stress, and liver histopathology in elderly rats with high-fat diet-induced liver damage.. Forty elderly male Wistar rats were randomly assigned to five groups (n = 8 in each): a normal diet (control), a high-fat diet (HFD), HFD + silymarin and vitamin C supplementation (HFD+Sup), HFD + swimming exercise (HFD+Exe), and HFD+Sup+Exe group (HFD+Sup+Exe). The non-alcoholic fatty liver model was induced for 6 wk in the HFD groups. After 6 wk of consuming an HFD, a daily supplemental gavage was administered to rats as an intervention along with HFD in the supplement groups for 8 wk. Moreover, rats in the exercise groups were subjected to swimming exercise training 5 d/wk for the same period.. The combination of swimming training and supplementation caused significant decreases in liver inflammatory biomarkers tumor necrosis factor-α and interleukin-1β while increasing total antioxidant capacity and peroxisome proliferator-activated receptor α (P < 0.05).. In elderly rats with liver injury caused by an HFD, the combination of exercise and silymarin with vitamin C supplementation effectively reduced oxidative stress, liver inflammation, fat accumulation, and regulated liver enzymes.

Topics: Aged; Animals; Ascorbic Acid; Diet, High-Fat; Dietary Supplements; Humans; Inflammation; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Silymarin; Swimming

There is no dietary strategy that has yet been specifically advocated for haemophilia. Therefore, we sought to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) diet in adolescents with haemophilia. In this parallel trial, forty male adolescents with haemophilia were dichotomised into the DASH group or control group for 10 weeks. The serum high sensitivity C-reactive protein, IL-6, complete blood count (CBC), serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, partial thromboplastin time (PTT), waist circumference (WC), percentage of body fat, fat-free mass and liver steatosis were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. The DASH diet was designed to include high amounts of whole grains, fruits, vegetables and low-fat dairy products, as well as low amounts of saturated fats, cholesterol, refined grains, sweets and red meat. Serum vitamin C in the DASH group was significantly increased compared with the control (

Topics: Adolescent; Ascorbic Acid; Blood Cell Count; Body Composition; Child; Dietary Approaches To Stop Hypertension; Hemophilia A; Humans; Hypertension; Inflammation; Liver; Male; Prothrombin Time

Vitamin C (VC), widely found in vegetables and fruits, operates as an electron donor to perform various biological functions including anti-inflammatory activity. However, the mechanisms by which VC inhibits inflammation remain insufficiently understood. Accordingly, we performed a detail mechanistic study on anti-inflammatory activity of VC at millimolar (pharmacological) concentrations in lipopolysaccharides-stimulated RAW264.7 cells. It was found that VC and its two-electron oxidative product, dehydroascorbate (DHA) constructs an efficient redox cycle with the aid of intracellular glutathione and copper ions, thereby facilitating the generation of reactive oxygen species (ROS) and the ROS-dependent inhibition against the NF-κB-mediated inflammation.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Inflammation; Lipopolysaccharides; Mice; NF-kappa B; RAW 264.7 Cells; Reactive Oxygen Species

Demyelination, inflammation, oxidative injury, and glial activation are the main pathological hallmarks of multiple sclerosis (MS). Vitamins, as essential micronutrients, seem to be crucial in the pathogenesis of MS, and particularly vitamins A and C were found to have a protective role in MS development or progression. In this study, the therapeutic potential of combined therapy of vitamins A and C on progression of experimental autoimmune encephalomyelitis (EAE) and myelin repair mechanisms was examined. EAE, an animal model of MS, was induced in female Lewis rats. The rats were treated with daily intraperitoneal injections of vitamins A and C and their combination. We found that co-supplementation of vitamins A and C mitigated neurological severity and EAE disease progression. Histological study confirmed a significant reduction in demyelination size, inflammation and immune cell infiltration as well as microglia and astrocyte activation following co-administration of vitamins A and C. Co-administration of vitamins A and C also decreased the levels of pro-inflammatory cytokines (TNF-α, IL1β) and iNOS and increased gene expressions of IL-10, Nrf-2, HO-1, and MBP. Combination therapy of vitamins A and C also increased the total antioxidant capacity and decreased levels of oxidative stress markers. Finally, we proved that co-administration of vitamins A and C has anti-apoptotic and neuroprotective impacts in EAE via decreasing caspase-3 and increasing BDNF and NeuN expressing cells. The present study suggests that combined therapy of vitamins A and C may be an effective strategy for development of alternative medicine in boosting myelin repair in demyelinating diseases.

Topics: Animals; Ascorbic Acid; Encephalomyelitis, Autoimmune, Experimental; Female; Inflammation; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Rats; Rats, Inbred Lew; Vitamin A; Vitamins

Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex [OR: 0.72, 95% CI: 0.54, 0.92]. A greater risk of MMD was associated with lower vitamin C intake [OR: 0.70, 95% CI: 0.48, 0.94] and increased fecal concentrations of MPO [OR: 1.31, 95% CI: 1.08, 1.51]. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Bayes Theorem; Birth Cohort; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Inflammation; Malnutrition; Micronutrients; Prevalence; Vitamin A Deficiency

The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism.. Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides.. AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1β, and IL-6 and regulating MDA, SOD, and GSH. In an. AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Topics: Alanine; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Aspartate Aminotransferases; Creatinine; Cytokines; Glutathione Peroxidase; Hydrocortisone; Inflammation; Interleukin-1beta; Interleukin-6; Malondialdehyde; Mice; NF-kappa B; Nitrogen; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Urea

Vitamin C deficiency, historically known as scurvy, was associated with sailors in the Victorian times, however, a global review in 2020 suggests it still exists in certain at-risk groups.A case is presented of a young non-verbal child with learning difficulties and on a restricted diet, in which the primary symptom was gingival inflammation. It posed a diagnostic dilemma due to the non-specific symptoms, and a delay in the diagnosis, until vitamin C deficiency was confirmed.Gingival inflammation is one of the common findings in vitamin C deficiency and dental professionals may be the first point of contact. The importance of dietary evaluation, identifying and looking for other signs and liaising with the medical colleagues are discussed.This case highlights the role of the dentist in identifying latent cases of vitamin C deficiency and to consider this as a differential diagnosis especially in certain at-risk groups.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Diagnosis, Differential; Humans; Inflammation; Scurvy

Novel N-substituted Indole derivatives with various hetero-cyclic moieties were synthesized via an ethyl linker in order to obtain highly potent anti-inflammatory and antioxidant agents. The structure of the obtained chemical compounds was determined using IR,

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Formaldehyde; Humans; Indoles; Inflammation; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship

Dysregulation of adipose tissue involves increased cellular hypoxia, ER stress, and inflammation and altered adipokine production, contributing to the aetiology of obesity-related diseases including type 2 diabetes and cardiovascular disease. This study aimed to investigate the effects of Vitamin C supplementation on these processes in primary human preadipocytes and adipocytes. Treatment of preadipocytes and adipocytes with the proinflammatory cytokine TNFα and palmitic acid (PA), to mimic the obesogenic milieu, significantly increased markers of hypoxia, ER stress and inflammation and reduced secretion of high molecular weight (HMW) adiponectin. Importantly, Vitamin C abolished TNFα+PA induced hypoxia and significantly reduced the increases in ER stress and inflammation in both cell types. Vitamin C also significantly increased the secretion of HMW adiponectin from adipocytes. These findings indicate that Vitamin C can reduce obesity-associated cellular stress and thus provide a rationale for future investigations.

Topics: Adipocytes; Adiponectin; Ascorbic Acid; Diabetes Mellitus, Type 2; Humans; Hypoxia; Inflammation; Obesity; Tumor Necrosis Factor-alpha

The ongoing crisis of antimicrobial resistance demands novel combinations between antimicrobials and nonantimicrobials to manage infections caused by highly resistant pathogens. This study aimed to evaluate the effect of combining sodium ascorbate and/or apo-transferrin with imipenem, forming double and triple combinations, against 20 multiple-carbapenemase-producing Acinetobacter baumannii strains using the checkerboard test, time-kill assay, and disc diffusion test. The results of the checkerboard assay revealed that all double combinations showed indifference, while only triple combination recorded a synergistic effect (fractional inhibitory concentration index [FICI] < 0.8) in 95% the test isolates. Moreover, the MIC of imipenem (MIC

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Ascorbic Acid; Biological Factors; Carbapenems; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Inflammation; Mice; Microbial Sensitivity Tests; Pneumonia; Transferrins

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C's influence on the development and progression of IBD in Gulo(-/-) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ-lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(-/-) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(-/-) mice to vitamin C-sufficient Gulo(-/-) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.

Topics: Animals; Antioxidants; Ascorbic Acid; Colitis; Cytokines; Dextran Sulfate; Humans; Inflammation; Inflammatory Bowel Diseases; Interleukin-22; Interleukin-6; Interleukins; L-Gulonolactone Oxidase; Mice; Mice, Inbred C57BL; Mucin-1; Mustelidae; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Vitamins

Population studies have shown a trend in decreasing vitamin C status and increasing prevalence of osteoporosis in patients with diabetes and non-diabetic people. Dietary vitamin C consumption is linked to improvement in bone mineral density (BMD) in epidemiological studies. VCAM-1 and adiponectin are known to activate osteoclasts, which increase bone loss.. This study examined whether there is any association between the circulating level of vitamin C and BMD and whether the beneficial effect of vitamin C on BMD was linked to a simultaneous decrease in circulating levels of adiponectin and VCAM-1 in subjects with diabetes.. Patients with diabetes (T2D,. Patients with diabetes had lower levels of vitamin C and higher levels of VCAM-1 and inflammatory cytokines. There was a significant positive association between vitamin C blood levels and lumbar spine BMD as well as a significant negative association between total adiponectin and VCAM-1 levels with that of vitamin C and lumbar BMD in patients with diabetes. Total adiponectin and VCAM-1 also showed a negative association with BMD of both the right and left femurs. The inter-relationship among the circulating levels of vitamin C and VCAM-1 and BMD was strong and is a novel finding.. This study reports a positive association of circulating vitamin C levels and the BMD and that the beneficial effects of vitamin C on BMD could be linked to a simultaneous lowering in circulating VCAM-1 and total adiponectin levels. Thus, dietary vitamin C consumption has potential to lower inflammation and the risk of osteoporosis in subjects with diabetes.

Topics: Absorptiometry, Photon; Adiponectin; Ascorbic Acid; Biomarkers; Bone Density; Cytokines; Diabetes Mellitus; Humans; Inflammation; Lumbar Vertebrae; Osteoporosis; Vascular Cell Adhesion Molecule-1; Vitamins

Obese or overweight is a risk factor for some chronic diseases, and oxidative stress and inflammation may be one of the molecular mechanisms leading to the persistence of these chronic diseases. Discovering interventions to alleviate oxidative stress and inflammation in the overweight/obese population, is very important for public health and health education.. A two-week panel intervention study (Run 0-Run 1-Run 2) was conducted. The subjects were 77 overweight/obese undergraduates attending Dali University, with a BMI>24 kg/m. The results demonstrated (1) Walking significantly alleviated ROS levels, and this was consistent in Run 1 and Run 2; (2) During Run1, all three intervention modes reduced levels of 8-OHdG, but there was a statistically insignificant increase during Run 2; (3) No alleviating effects of the three intervention modes on TNF-α levels during Run 1 and Run 2 were observed; (4) The alleviating effects of the three intervention modes on IL-1β levels during Run 1 and Run 2 were clear.. Walking and taking vitamin C can reduce levels of ROS, 8-OHdG and IL-1β, but not TNF-α, in overweight/obese participants. These interventions may become potential preventive measures for the overweight against obese-induced oxidative stress and inflammation.

Topics: Ascorbic Acid; Humans; Inflammation; Obesity; Overweight; Oxidative Stress; Reactive Oxygen Species; Students; Tumor Necrosis Factor-alpha; Walking

Cardiac injury is common and associated with poor clinical outcomes in COVID-19. Data are lacking whether high-dose intravenous vitamin C (HIVC) could help to ameliorate myocardial injury in the pandemic.. The retrospective cohort study included consecutive severe and critically ill COVID-19 patients with cardiac injury receiving symptomatic supportive treatments alone or together with HIVC. Troponin I and inflammatory markers were collected at admission and day 21 during hospitalization from the electronic medical records.. The patients (n = 113) were categorized into the ameliorated cardiac injury (ACI) group (n = 70) and the non-ameliorated cardiac injury (NACI) group (n = 43). Overall, fifty-one (45.1%) patients were administered with HIVC, the percentages of patients with HIVC were higher in the ACI group than those in the NACI group. Logistic regression analysis revealed that HIVC was independently associated with the improvement of myocardial injury. Further analysis showed that inflammatory markers levels significantly decreased at day 21 during hospitalization in patients with HIVC therapy compared to those administered with symptomatic supportive treatments alone. Meanwhile, similar results were also observed regarding changes in inflammatory markers levels from baseline to day 21 during hospitalization in the patients treated with HIVC.. HIVC can ameliorate cardiac injury through alleviating hyperinflammation in severe and critically ill patients with COVID-19.

Topics: Aged; Ascorbic Acid; Biomarkers; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Female; Heart Injuries; Hospitalization; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Pandemics; Retrospective Studies; Troponin I

This study examined the effects of injectable vitamin C (VC) before transport and duration of transit on feedlot performance, inflammation, and muscle fatigue in cattle. One hundred thirty-two Angus-cross steers (393 ± 4 kg) were stratified by body weight (BW) to a 2 × 2 factorial of intramuscular injection (INJ; 20 mL/steer): VC (250 mg sodium ascorbate/mL) or saline (SAL) and road transit duration (DUR): 18 h (18-h; 1,770 km) or 8 h (8-h; 727 km). On day 0, steers were weighed and given INJ of VC or SAL immediately before transport. Upon return (day 1), BW and blood were collected before steers returned to pens equipped with GrowSafe bunks. Steers were weighed on days 0, 1, 7, 15, 30, 31, 54, and 55. Data were analyzed via ProcMixed of SAS (experimental unit = steer; 32 to 34 steers/treatment) with fixed effects of INJ, DUR, and the interaction. Blood was collected on days -5, 1, 2, 3, and 7 (n = 9 steers/treatment); blood parameters were analyzed as repeated measures with the repeated effect of day. Area under the curve (AUC) for plasma ferric reducing antioxidant power (FRAP) was calculated using R. Final BW was greater for 8 h compared to 18 h (P = 0.05) with no effect of INJ or interaction (P ≥ 0.51). Dry matter intake (DMI) from days 1 to 7 was greater for VC-8, intermediate for VC-18 and SAL-18, and least for SAL-8 (P = 0.02). Overall, DMI tended to be greatest for SAL-18, intermediate for VC-18 and VC-8, and least for SAL-8 (P = 0.08). Days 7 to 31 gain:feed (G:F) was greatest for VC-18 compared to other treatments (INJ × DUR, P = 0.05), and there was no effect of treatment on overall G:F (P ≥ 0. 19). There was no INJ or INJ × DAY (P ≥ 0.17) effect on serum lactate, haptoglobin, or non-esterified fatty acid. However, these blood parameters were greater on day 1 for 18 h compared to 8 h, and both treatments returned to near baseline by day 3 (DUR × DAY, P < 0.01). Plasma ascorbate concentrations on day 1 were greater for VC compared to SAL and returned to baseline by day 2 (INJ × DAY, P < 0.01). Plasma FRAP AUC from days -5 to 3 was greatest for VC-18, intermediate for VC-8 and SAL-8, and least for SAL-18 (INJ × DAY, P = 0.02). This suggests an antioxidant prior to long-haul transit positively influenced antioxidant capacity; however, VC did not improve overall post-transit performance. Although longer transit duration increased indicators of muscle fatigue and inflammation, post-transit performance was not appreciably different between transit du

Topics: Animal Feed; Animals; Ascorbic Acid; Cattle; Cattle Diseases; Diet; Dietary Supplements; Inflammation; Muscle Fatigue

Obesity is associated with an increased risk of metabolic abnormalities. The citrus fruit calamondin contains nobiletin and hesperidin, which are involved in lipid metabolism, and vitamin C, which is an antioxidant. We investigated the metabolic profiles of C57BL/6 mice fed a normal diet, high-fat diet (HFD), HFD + 1% (w/w) calamondin puree (HFD + CL1), or HFD + 5% (w/w) calamondin puree (HFD + CL5). Glucose tolerance was significantly higher in HFD + CL than in HFD-fed mice. Histological analysis revealed less lipid accumulation in the livers of HFD + CL-fed mice than in those of HFD-fed control mice. Hepatocyte ballooning and large lipid droplets - key non-alcoholic fatty liver disease characteristics - were observed in HFD-fed mice after 4 weeks; however, they were nearly absent in HFD + CL-fed mice. The serum expression level of inflammation-associated Ccl2 was lower in HFD + CL-fed mice than in HFD-fed mice. Thus, calamondin may ameliorate HFD-induced metabolic disturbances, including the progression of non-alcoholic fatty liver disease.

Topics: Adipose Tissue; Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Body Weight; Chemokine CCL2; Citrus; Diet; Diet, High-Fat; Dietary Supplements; Gene Expression; Inflammation; Insulin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity

Although hepcidin synthesis is stimulated by inflammation and inhibited by Fe deficiency, the strength of their opposing effects on serum hepcidin (SHep) in humans remains unclear. It was recently shown that an inflammatory stimulus in anaemic women did not increase SHep or decrease Fe absorption. The enhancing effect of ascorbic acid on Fe absorption may not be effective during inflammation because of increased SHep. Our study aim was to test whether reducing inflammation in Fe-depleted overweight (OW) women with low-grade inflammation would lower SHep and improve Fe absorption with and without ascorbic acid, compared with normal-weight (NW) women without inflammation. Before and after 14 d of anti-inflammatory treatment (3 × 600 mg ibuprofen daily) in OW and NW women (n 36; 19-46 years of age), we measured SHep and fractional Fe absorption (FIA) (erythrocyte Fe incorporation) from 57Fe- and 58Fe-labelled test meals with and without ascorbic acid. There were significant group effects on IL-6, C-reactive protein, serum ferritin and SHep (for all, P < 0·05). There was a significant treatment effect on SHep (P < 0·05): in OW women, treatment decreased IL-6 by approximately 30 % and SHep by approximately 45 %. However, there were no significant treatment or group effects on FIA. Body Fe stores (BIS) were a significant positive predictor of SHep before and after treatment (P < 0·001), but IL-6 was not. Reducing chronic inflammation in OW women halved SHep but did not affect Fe absorption with or without ascorbic acid, and the main predictor of Fe absorption was BIS.

Topics: Adult; Ascorbic Acid; Female; Hepcidins; Humans; Ibuprofen; Inflammation; Interleukin-6; Intestinal Absorption; Iron; Middle Aged; Overweight; Young Adult

Oxidative stress is one of the possible mechanisms in vancomycin (VCM) induced nephrotoxicity. Some studies suggested that high dose Vitamin C (VC) has protective effect against the nephrotoxicity in mice, but the underlying molecular mechanism is not mentioned. We investigated the potential targets of high dose VC against oxidative stress and inflammation induced by VCM in renal tubular epithelial cells.. We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2).. VCM added to HK-2 cells caused an increase of cell death, oxidative stress and expression of inflammatory cytokines. Co-treatment with 0.5 and 1 mM VC attenuated 4-8 mM VCM induced cell death and increased the cell viability to 58-90%. VC significantly decreased lipid peroxidation and increased superoxide dismutase activity. The upregulations of NF-κB, TNF-α and IL-6 in HK-2 cells under 4 mM VCM were also reversed by 0.5 mM VC through the inhibition of oxidative stress.. This study showed for the first time that VC can attenuate the VCM induced nephrotoxicity by decreasing lipid peroxidation and expression of inflammatory cytokines, and increasing superoxide dismutase 2 (SOD2) activity, this effect may relate to the regulation of ROS/NF-κB pathway.

Topics: Animals; Ascorbic Acid; Inflammation; Kidney; Mice; Oxidative Stress; Vancomycin

Chlorpyrifos (CPF) is an extensive environmental contaminant and disrupts the physiological status of living organisms. CPF is found to hinder the health of aquatic organisms and ecological function in aquatic systems. The current study aimed at evaluating the protective effects of vitamin C (VC) on the immune response, hematological parameters, and histopathological alterations in Nile tilapia exposed to CPF. Nile tilapia were exposed to waterborne CPF (15 μg/L) for 30 days. Fish were divided into control group: received basal diet; CPF group: received basal diet and exposed to waterborne CPF; VC group: received basal diet plus 0.8 mg VC/kg; and CPF/VC group: received basal diet plus 0.8 mg VC/kg and exposed to waterborne CPF. Blood samples were taken after 15 days and 30 days of the treatment. Liver, gills, and intestine tissues were collected on the 30th day of treatment. CPF showed a deleterious effect on fish's growth performance; it decreased the weight gain by 6%, while VC increased it by 17-23% compared to the control group. CPF group recorded the lowest survival rate (83%), while VC achieved survivability of 96.7% and 93.3% in VC and CPF/VC groups, respectively. The blood picture revealed moderate changes in the CPF group, where the marked alteration was in the hemoglobin concentration and white blood cells. CPF disrupted the hepatic and renal function. Serum lysozyme activity, phagocytic activity, and phagocytic index displayed a dramatic decline in the CPF group but enhanced in VC and CPF/VC groups. An upregulation was observed in antioxidant genes (catalase and glutathione peroxidase), heat shock protein 70, caspase-3, and the cytokines interleukin 1β, interleukin 8, and interferon-gamma in the CPF group. Simultaneously, moderate or normal levels were shown in the VC and CPF/VC groups. CPF altered the histoarchitecture of gills, intestine, and hepatopancreas with apparent degenerative changes possibly resulted from the oxidative stress. At the same time, VC retained the normal structure of the studied tissues. This study raises concerns about the safety of CPF and its impact on the aquatic environment. VC has a high potential to restore the normal physiology of fish exposed to CPF.

Topics: Animals; Antioxidants; Ascorbic Acid; Chlorpyrifos; Cichlids; Immunosuppression Therapy; Inflammation; Oxidative Stress

Colistin is a potent antibiotic which is mainly preferred in the treatment of multidrug-resistant (MDR) gram-negative bacilli. However, due to the increased risk of acute kidney injury following its use, the clinical application is limited. This nephrotoxicity is known to be induced by oxidative stress and related inflammation. In this study on rats, potent antioxidants Dexpanthenol (DEX) and Ascorbic acid (Vit C) have been administered in combination with Colistin to find out whether they would weaken Colistin's nephrotoxic effects.. Inflammation biomarkers were studied with enzyme-linked immunosorbent assay (ELISA) kits, and oxidative stress biomarkers were studied with different photometric methods in blood and tissue samples taken after treatment with DEX and Vit C in rats with colistin nephrotoxicity. In addition, inflammation and necrosis in the kidney tissues were examined pathologically.. It has been observed in the serum and tissue samples that DEX and Vit C decrease oxidative stress and inflammation biomarkers, therefore acting as nephroprotective agents.. These compounds have been found to ameliorate the nephrotoxic effects of Colistin, which were demonstrated in the rats treated with Colistin, as well as the combinations.

Topics: Acute Kidney Injury; Animals; Ascorbic Acid; Colistin; Disease Models, Animal; Inflammation; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxidative Stress; Pantothenic Acid; Rats; Rats, Sprague-Dawley

Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-β, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.

Topics: Animals; Antioxidants; Ascorbic Acid; Fibrosis; Hyperuricemia; Inflammation; Kidney Diseases; Male; Oxonic Acid; Rats; Rats, Sprague-Dawley

Inflammation is a risk factor for the onset and progression of schizophrenia, and dietary factors are related to chronic inflammation. We investigated whether the dietary inflammatory index (DII) is associated with schizophrenia in the Korean population. Of the 256 subjects who responded to the questionnaire, 184 subjects (117 controls; 67 individuals with schizophrenia) were included in this case-control study. A semi-quantitative food frequency questionnaire was used to evaluate the dietary intakes of the study participants. The energy-adjusted DII (E-DII) was used to assess the inflammatory potential of the participants' diets. Dietary intakes of vitamin C, niacin, and folate were significantly reduced in the patients with schizophrenia. The patients with schizophrenia had higher E-DII scores than the controls (

Topics: Adolescent; Adult; Ascorbic Acid; Case-Control Studies; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Female; Folic Acid; Humans; Inflammation; Male; Micronutrients; Middle Aged; Niacin; Republic of Korea; Schizophrenia; Vitamins; Young Adult

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the

Topics: Animals; Ascorbic Acid; Blood-Brain Barrier; Cognitive Dysfunction; Disease Models, Animal; Dose-Response Relationship, Drug; Heme Oxygenase (Decyclizing); Hippocampus; Inflammation; Male; NF-E2-Related Factor 2; Oxidative Stress; Protective Agents; Rats, Sprague-Dawley; Sepsis

The treatment of diabetes mellitus aftermaths became one of medicine's most significant therapeutical and financial issues in the XXI century. Most of which are related to protein glycation and oxidative stress caused by long lasting periods of hyperglycemia. Thus, even within a venerable one, searching for new drugs, displaying anti-glycation and anti-oxidative properties seem useful as an additive therapy of diabetes. In this paper, we assessed the anti-glycating properties of phloroglucinol, a drug discovered in the XIX century and still used in many countries for its antispasmodic action. Herewith, we present its effect on protein glycation, glycoxidation, and oxidative damage in an albumin glycation/oxidation model and HepG2 cells treated with high glucose concentrations. The phloroglucinol showed the strongest and the widest protective effect within all analyzed antiglycating (aminoguanidine, pioglitazone) and anti-oxidative (vitamin C, GSH) agents. To the very best of our knowledge, this is the first study showing the properties of phloroglucinol in vitro what once is proven in other models might deepen its clinical applications.

Topics: Albumins; Antioxidants; Ascorbic Acid; Glucose; Glycation End Products, Advanced; Guanidines; Hep G2 Cells; Hepatocytes; Humans; Inflammation; Nitrosative Stress; Oxidative Stress; Phloroglucinol; Pioglitazone; Reactive Oxygen Species

Ten patients with scurvy were evaluated by rheumatology; we review their clinical, laboratory, and dietary presentations. Eight patients had developmental delay or autism. All had elevated inflammatory markers. These clinical and laboratory features with imaging findings can mimic rheumatic conditions such as arthritis, vasculitis, and chronic nonbacterial osteomyelitis (CNO).

Topics: Adolescent; Arthritis, Juvenile; Ascorbic Acid; Ascorbic Acid Deficiency; Autistic Disorder; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Diagnosis, Differential; Diet; Female; Humans; Inflammation; Male; Musculoskeletal Pain; Osteomyelitis; Rheumatology; Scurvy; Vasculitis; Young Adult

Children are at high risk of injuries and wounds. The application of medical grade honey is a promising approach to improving the healing of wounds of various origin and severity. However, the use of medical grade honey in young paediatric patients remains limited. The aim of this study is to show the safety, efficacy and usefulness of medical grade honey in abdominal wounds, of different causes, in paediatric patients.. This was a prospective, observational case series evaluating five young infants with abdominal wounds at the General Hospital in Thessaloniki. All wounds were treated in the same manner with daily medical grade honey applied to the wound area and closely monitored.. All treated wounds rapidly presented granulation tissue formation and underwent re-epithelialisation. Peripheral oedema and inflammation decreased upon initial application. Necrotic tissue was effectively debrided when present. Slough was removed and no signs of infection were detected, irrespective of initial wound presentations. Scar formation was minimal and the full range of motion was preserved in all cases.. Based on this case study, medical grade honey is safe and effective in treating different abdominal wounds, including infected or dehisced wounds as well as burns. The easy application and broad applicability make medical grade honey recommendable as a first-line treatment in paediatric patients.

Topics: Abdominal Injuries; Apitherapy; Appendectomy; Appendicitis; Ascorbic Acid; Bacteroides Infections; Burns; Burns, Chemical; Child; Child, Preschool; Dermatologic Agents; Drug Resistance, Multiple, Bacterial; Edema; Female; Gastrostomy; Greece; Honey; Humans; Infant; Infant, Newborn; Inflammation; Klebsiella Infections; Lanolin; Male; Neuroblastoma; Oils, Volatile; Ointments; Prospective Studies; Re-Epithelialization; Retroperitoneal Neoplasms; Surgical Wound Dehiscence; Surgical Wound Infection; Vitamin E; Vitamins; Zinc Oxide

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. The health-beneficial, particularly anti-inflammatory effects of vitamin C (ascorbate) are well known. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10

Topics: Acute Disease; Animals; Apoptosis; Ascorbic Acid; Campylobacter Infections; Campylobacter jejuni; Colon; Enterocolitis; Inflammation; Inflammation Mediators; Interleukin-10; Mice, Inbred C57BL; Treatment Outcome

Topics: Ascorbic Acid; Biomarkers; Humans; Inflammation; Respiratory Insufficiency; Sepsis; Vascular System Injuries

Topics: Ascorbic Acid; Biomarkers; Humans; Inflammation; Respiratory Insufficiency; Sepsis; Vascular System Injuries

Using rats, we previously found that vitamin C deficiency increases serum levels of interleukin-6 (IL-6) and glucocorticoid, and changes the gene expression of acute phase proteins (APP) in the liver. However, it remains unclear how vitamin C deficiency causes these inflammation-like responses. In this study, we investigated the possibility that changes in gut microbiota are involved in the induction of APP gene expression by vitamin C deficiency. ODS rats that cannot genetically synthesize vitamin C were divided into 4 groups based on the presence or absence of vitamin C or antibiotics and were raised for 15 d. Neomycin, vancomycin, and ampicillin were used as antibiotics, and 300 mg L-ascorbic acid/kg was added to the AIN93G diet. Vitamin C deficiency affected neither the wet tissue weights nor relative abundance of bacteria in the cecal contents. Antibiotic administration increased wet weights of the cecum, cecal contents, and colon, changed the relative abundance of some bacteria in the cecal contents, and decreased serum IL-6 level. However, antibiotic administration had no effect on serum concentrations of corticosterone and α1-acid glycoprotein (AGP), vitamin C concentration in the liver, and mRNA levels of haptoglobin and AGP in the liver. Therefore, disturbance of gut microbiota did not attenuate the increase in glucocorticoid level and induction of APP gene expression due to vitamin C deficiency. This suggests that gut microbiota is not involved in the inflammation-like responses caused by vitamin C deficiency.

Topics: Acute-Phase Proteins; Animals; Anti-Bacterial Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Corticosterone; Gastrointestinal Microbiome; Inflammation; Interleukin-6; Liver; Male; Rats; RNA, Messenger

Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles in the brain. Despite a recent interest in vitamin C therapies for critical care medicine, little is known about vitamin C regulation during acute inflammation and critical illnesses such as sepsis. Using a cecal slurry (CS) model of sepsis in mice, we determined ASC and inflammatory changes in the brain following the initial treatment. ASC levels in the brain were acutely decreased by approximately 10% at 4 and 24 h post CS treatment. Changes were accompanied by a robust increase in liver ASC levels of up to 50%, indicating upregulation of synthesis beginning at 4 h and persisting up to 7 days post CS treatment. Several key cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNFα), and chemokine (C-X-C motif) ligand 1 (CXCL1, KC/Gro) were also significantly elevated in the cortex at 4 h post CS treatment, although these levels returned to normal by 48 h. These data strongly suggest that ASC reserves are directly challenged throughout illness and recovery from sepsis. Given the timescale of this response, decreases in cortical ASC are likely driven by hyper-acute neuroinflammatory processes. However, future studies are required to confirm this relationship and to investigate how this deficiency may subsequently impact neuroinflammation.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Cytokines; Disease Models, Animal; Inflammation; Mice; Mice, Inbred C57BL; Organ Specificity; Sepsis

Genetic and nutritional factors play an important role in inflammatory response and diseases. CXCL10 is a critical biomarker that is involved in multiple inflammatory diseases, and elevated levels of CXCL10 have been associated with the development of several chronic and infectious diseases. In contrast, micronutrients can attenuate inflammatory responses. Single nucleotide polymorphisms in the pro-inflammatory cytokine genes such as. This study aims to identify the modifying effect of nutritional factors on the association between. Participants (. CXCL10 levels were not different across different. The association between

Topics: alpha-Tocopherol; Ascorbic Acid; Biomarkers; Canada; Chemokine CXCL10; Cross-Sectional Studies; Female; Genotype; Humans; Inflammation; Interleukin-1beta; Male; Micronutrients; Nutrigenomics; Nutritional Status; Polymorphism, Single Nucleotide; Vitamin D; Young Adult

Vitamin C levels are decreased in arthritis patients and reduced levels following surgery may impair adequate healing.. This study measured changes in vitamin C and inflammatory markers in patients undergoing total knee arthroplasty (TKA).. Venous blood samples were collected from 10 patients during the preoperative to postoperative period. Vitamin C, interleukin-1. No significant changes in vitamin C levels were measured. However, all participants had suboptimal preoperative vitamin C levels and 90% had suboptimal levels postoperatively. IL-6 and CRP levels significantly increased during the immediate postoerative period.. There was a rise in inflammation following TKA while vitamin C levels did not significantly change during this short study period. Of note, every patient had suboptimal vitamin C levels prior to surgery and 90% continued with suboptimal levels two days postoperatively.

Topics: Aged; Aged, 80 and over; Arthritis; Arthroplasty, Replacement, Knee; Ascorbic Acid; Biomarkers; C-Reactive Protein; Cytokines; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Male; Middle Aged; Postoperative Period; Prospective Studies

Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitivity (IS), a cardinal MetS feature, the principal aim of the present work is to determine whether glycomacropeptide (GMP), a milk-derived bioactive peptide, exerts beneficial effects on their expression.. Fully differentiated intestinal Caco-2/15 cells are used to evaluate the preventive action of 2 mg/mL GMP against OxS and inflammation induced by the mixture iron-ascorbate (Fe/Asc) (200 μM:2 mM). The potency of GMP of decreasing the production of lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) is also assessed.. The administration of GMP significantly reduces malondialdehyde, a biomarker of lipid peroxidation, and raises superoxide dismutase 2 and glutathione peroxidase via the induction of the nuclear factor erythroid 2-related factor 2, a transcription factor, which orchestrates cellular antioxidant defenses. Similarly, GMP markedly lowers the inflammatory agents tumor necrosis factor-α and cyclooxygenase-2 via abrogation of the nuclear transcription factor-kB. Moreover, GMP-treated cells show a down-regulation of Fe/Asc-induced mitogen activated protein kinase pathway, suggesting greater IS. Finally, GMP decreases the production of CM, VLDL, and LDL.. Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP.

Topics: Ascorbic Acid; Caco-2 Cells; Caseins; Glutathione Peroxidase; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Intestinal Mucosa; Iron; Lipoproteins; Malondialdehyde; Metabolic Syndrome; Mitogen-Activated Protein Kinases; Oxidative Stress; Peptide Fragments; Superoxide Dismutase

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Coronavirus; Coronavirus Infections; Curcuma; Curcumin; Cytokines; Drug Combinations; Drug Delivery Systems; Gene Ontology; Glycyrrhiza; Glycyrrhizic Acid; Humans; Immunity, Innate; Inflammation; Interferons; Plant Extracts; Signal Transduction; Systems Biology; T-Lymphocytes; Vitamins

Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.

Topics: Aging; Animals; Ascorbic Acid; Dehydroascorbic Acid; Gene Expression Regulation; Glucose Transporter Type 1; Humans; Inflammation; Kidney; Mice; Oxidative Stress; Sodium-Coupled Vitamin C Transporters

The antioxidant and anti-inflammatory properties of Malpighia emarginata D.C (acerola) and Camellia sinensis L. (green tea) have been studied, particularly as an alternative in medicinal approach for different physio pathological conditions. Here we develop an powder blend formulated with both Malpighia emarginata D.C and Camellia sinensis L. which have in the composition higher content of ascorbic acid and epigallatocathechin-3-gallate respectively. Using different conditions for microencapsulation of biocompounds, we performed the powder production through spray-drying process. After, we evaluate the antioxidant and anti-inflammatory properties of blends formulated with Malpighia emarginata D.C and Camellia sinensis L. in an in vitro model of inflammation, using LPS-stimulated RAW-264.7 macrophage cell line. We observed that co-treatment with blends was able to modulate the redox parameters in cells during the in vitro inflammatory response. Moreover, the co-treatment with blends were able to modulate inflammatory response by altering the secretion of cytokines IL-1β, IL-6, IL-10, and TNF-α. Taken together, our results demonstrate for the first time the synergistic effects antioxidant and anti-inflammatory of Malpighia emarginata D.C and Camellia sinensis L. These results warrant further use of the blend powder for use in the products to heath beneficial, principally in terms of prevention of chronic diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Camellia sinensis; Catechin; Cytokines; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Malpighiaceae; Mice; Plant Extracts; RAW 264.7 Cells

To date, there are no recommendations about screening plasma vitamin C concentration and adjust its supplementation in patients on long-term home parenteral nutrition (HPN). The aim of this study was to evaluate vitamin C status and determine if a commercial multivitamin preparation (CMVP) containing 125 mg of vitamin C is sufficient in stable patients on HPN. All clinically stable patients receiving HPN or an intravenous fluid infusion at least two times per week for at least 6 months, hospitalized for nutritional assessment, were retrospectively included, for a total of 186 patients. We found that 29% of the patients had vitamin C insufficiency (i.e., <25 µmol/L). In univariate analysis, C-reactive protein (CRP) (

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Eating; Female; Humans; Inflammation; Male; Middle Aged; Monitoring, Physiologic; Nutrition Assessment; Nutritional Physiological Phenomena; Nutritional Status; Parenteral Nutrition, Home Total; Retrospective Studies

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). However, the intervention dose of Vc, and the prophylactic and therapeutic effects on NAFLD are unclear. This study aimed to investigate the prophylactic and therapeutic effects of low (LVc), medium (MVc) and high (HVc) doses of Vc on NAFLD. C57BL/6 mice were randomly assigned to prophylactic groups (mice received a high-fat diet (HFD) concomitant with different doses of Vc) and therapeutic groups (HFD-induced NAFLD mice treated with different doses of Vc). Results showed that prophylactic LVc and MVc administration reduced the risk of NAFLD development in HFD-fed mice, as evidenced by significantly lowered body weight, perirenal adipose tissue mass, and steatosis, whereas prophylactic HVc administration did not prevent HFD-induced NAFLD development. Furthermore, therapeutic MVc administration significantly ameliorated HFD-induced increase in body weight, perirenal adipose tissue mass and steatosis, whereas therapeutic LVc and HVc administration did not ameliorate NAFLD symptoms. In fact, therapeutic HVc administration significantly increased body weight, perirenal adipose tissue mass, and lobular inflammation. Moreover, prophylactic LVc administration was more effective than therapeutic LVc administration as evidenced by significantly lower body weight, perirenal adipose tissue mass, steatosis, ballooned hepatocytes, and lobular inflammation in prophylactic LVc administration. The same trends were observed between prophylactic HVc administration and therapeutic HVc administration. In addition, all Vc-administered mice exhibited low blood glucose, triglycerides and homeostasis model assessment of insulin resistance values and high adiponectin levels compared to HFD-fed mice. Our study suggested that MVc was beneficial for HFD-induced NAFLD prophylaxis and therapy. LVc prevented HFD-induced NAFLD development, while HVc for NAFLD management was risky. This study offers valuable insight into the effect of various Vc doses on NAFLD management.

Topics: Adiponectin; Animals; Antioxidants; Ascorbic Acid; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Triglycerides; Weight Gain

Inflammation is our body's normal defense mechanism, but in some cases, it may be responsible for causing different kinds of disorders. Several antiinflammatory drugs are present for the treatment of these disorders; however, the conventional anti-inflammatory drugs cause side effects when used in the long term and therefore, it is better to use them in a low dose for a shorter duration of time. This study was designed to find out whether there is an augmentation of the therapeutic effectiveness of the antiinflammatory drugs like diclofenac sodium (NSAID), prednisolone (steroid) and atorvastatin (statin) when used in combination with ascorbic acid (antioxidant).. Wistar Rats (n=144) were selected and divided into 24 groups of 6 rats in each. Carrageenan and formalin were used to induce local inflammation and neuropsychiatric effects, respectively. The inhibitions of such responses were measured after administering a drug alone and in combination with ascorbic acid.. In case of carrageenan mediated inflammation, the combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave the highest inhibition of 74.19% compared to other groups of drugs. The combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave 97.25% inhibition for formalin-mediated inflammation group. In both cases, combination therapy showed statistically significant anti-inflammatory activities compared to monotherapy (p values <0.05).. All the data clearly indicate new combinations of drug therapy comprising diclofenac sodium, prednisolone, atorvastatin with ascorbic acid, which may be more effective against both local edema and the neuropsychiatric effect caused due to inflammation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Atorvastatin; Diclofenac; Disease Models, Animal; Drug Combinations; Drug Dosage Calculations; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Prednisolone; Rats; Treatment Outcome

Although it is now well established that heart failure with preserved ejection fraction (HFpEF) is associated with marked inflammation and a prooxidant state that is accompanied by vascular dysfunction, whether acute antioxidant (AO) administration can effectively target these disease-related decrements has not been evaluated. Thus, the present study sought to evaluate the efficacy of an acute over-the-counter AO cocktail (600 mg α-lipoic acid, 1,000 mg vitamin C, and 600 IU vitamin E) to mitigate inflammation and oxidative stress, and subsequently improve nitric oxide (NO) bioavailability and vascular function, in patients with HFpEF. Flow-mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit vessel and microvascular function, respectively, 90 min after administration of either placebo (PL) or AO in 16 patients with HFpEF (73 ± 10 yr, EF 54-70%) using a double-blind, crossover design. Circulating biomarkers of inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde and protein carbonyl), free radical concentration (EPR spectroscopy), antioxidant capacity, ascorbate and NO bioavailability (plasma nitrate, [Formula: see text], and nitrite, [Formula: see text]) were also assessed. FMD improved following AO administration (PL: 3.49 ± 0.7%, AO: 5.83 ± 1.0%), whereas RH responses were similar between conditions (PL: 428 ± 51 mL, AO: 425 ± 51 mL). AO administration decreased CRP (PL: 4,429 ± 705 ng/mL, AO: 3,664 ± 520 ng/mL) and increased ascorbate (PL: 30.0 ± 2.9 µg/mL, AO: 45.1 ± 3.7 µg/mL) and [Formula: see text] (PL: 182 ± 21 nM, AO: 213 ± 24 nM) but did not affect other biomarkers. Together, these data suggest that acute AO administration can exert anti-inflammatory effects and improve conduit artery vasodilation, but not microvascular function, in patients with HFpEF.

Topics: Antioxidants; Ascorbic Acid; Endothelium, Vascular; Heart Failure; Humans; Hyperemia; Inflammation; Oxidative Stress; Stroke Volume; Ventricular Function, Left; Vitamin E

The combination of ascorbic acid and rutin, often used in oral preparations, due to antioxidant and anti-inflammatory properties, can be used to protect skin cells against the effects of UV radiation from sunlight. Therefore, the aim of this study was to investigate the synergistic effect of rutin and ascorbic acid on the proteomic profile of UVA and UVB irradiated keratinocytes cultured in a three-dimensional (3D) system. Results showed that the combination of rutin and ascorbic acid protects skin cells against UV-induced changes. In particular, alterations were observed in the expression of proteins involved in the antioxidant response, DNA repairing, inflammation, apoptosis, and protein biosynthesis. The combination of rutin and ascorbic acid also showed a stronger cytoprotective effect than when using either compound alone. Significant differences were visible between rutin and ascorbic acid single treatments in the case of protein carboxymethylation/carboxyethylation. Ascorbic acid prevented UV or rutin-induced protein modifications. Therefore, the synergistic effect of rutin and ascorbic acid creates a potentially effective protective system against skin damages caused by UVA and UVB radiation.

Topics: Anti-Inflammatory Agents; Antioxidants; Apoptosis; Ascorbic Acid; Cells, Cultured; Cytoprotection; DNA Repair; Humans; Inflammation; Keratinocytes; Molecular Conformation; Protein Biosynthesis; Proteomics; Rutin; Skin; Sunlight; Ultraviolet Rays

Topics: Ascorbic Acid; Biomarkers; Humans; Inflammation; Respiratory Distress Syndrome; Respiratory Insufficiency; Sepsis; Vascular System Injuries

Topics: Ascorbic Acid; Biomarkers; Humans; Inflammation; Respiratory Distress Syndrome; Respiratory Insufficiency; Sepsis; Vascular System Injuries

Hyperglycemia-induced inflammation can greatly increase the risk of periodontal disease in people with diabetes. Low-level laser irradiation (LLLI) has been used for wound healing and anti-inflammation in many cases, and LLLI is known to inhibit the lipopolysaccharide (LPS)-stimulated inflammatory response. However, the therapeutic effect of LLLI in diabetes patients with periodontitis remains unknown. In this study, we cultured human gingival fibroblasts (HGFs) in high-glucose medium (35 mM) to mimic a hyperglycemic environment, and then measured the anti-inflammatory effect of LLLI by assessing the expression of pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 by quantitative real-time polymerase chain reaction. The results demonstrated no significant inflammatory response in HGFs cultured in mannitol medium and in those treated only with LLLI. However, HGFs cultured only in high-glucose medium showed significantly higher expression of pro-inflammatory cytokine than in those treated together with LLLI. We then observed that LLLI reduced the expression of pro-inflammatory cytokines in HGFs cultured in high-glucose medium by modulating cAMP signaling. We also investigated whether antioxidant (vitamin C) treatment reduced the inflammatory effect of oxidative stress in HGFs cultured in high-glucose medium but found no additive effect upon co-treatment with LLLI, suggesting that LLLI may activate cAMP signaling, but not reactive oxygen species (ROS) signaling, to reduce the high glucose-induced inflammation. In conclusion, LLLI may have an anti-inflammatory effect on HGFs in a high glucose environment and may benefit the treatment of periodontal disease in diabetes patients.

Topics: Ascorbic Acid; Cell Death; Cell Survival; Cells, Cultured; Cytokines; Fibroblasts; Gingiva; Humans; Hyperglycemia; Inflammation; Inflammation Mediators; Low-Level Light Therapy; RNA, Messenger

In our previous studies, vitamin C (VC) exerts potent pharmacological activities against liver injury (LI). Therefore, this report was designed to use network pharmacology-based strategy to predict therapeutic targets of VC against LI, and further to investigate the pharmacological molecular mechanisms. Pathological targets of LI were identified, followed by acquisition of verified targets of VC. After constructing target-functional protein interaction network of VC against LI, the core therapeutic targets of VC against LI were obtained. Further, biological function and pathway enrichment analyses were performed on core therapeutic targets to evaluate the biological processes and key signaling pathways of VC against LI. As revealed in network pharmacology assays, 6 key therapeutic targets for VC against LI were identified, showing tumor necrosis factor (TNF), nuclear factor-kappa-B p65 (RELA), nuclear factor-kappa-B p105 (NFKB1), TNF receptor-associated factor 2 (TRAF2), interleukin 6 (IL-6) and interleukin 1 beta (IL1B). On the basis of data analyses from DAVID database and omicshare cloud platform, bio-functional enrichment assays showed that the therapeutic effects of VC against LI were closely associated with regulating inflammatory reaction and apoptosis. Further, pathway enrichment analysis indicated the anti-LI benefits of VC were principally implicated in regulating the top 20 signaling pathways, such as inflammation-associated TNF signaling pathway, NF-κB signaling pathway. Taken together, the bioinformatics data elucidate that anti-LI pharmacological activities of VC may be predominantly related to inhibition of inflammatory stress, contributing to suppression of LI development. These resultant findings highlight the predicted therapeutic targets may be potential biomarkers for anti-LI.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Liver Diseases; Molecular Targeted Therapy; NF-kappa B; Pharmacology; Protein Interaction Maps; Signal Transduction; TNF Receptor-Associated Factor 2; Tumor Necrosis Factor-alpha

An oxidant/antioxidant disequilibrium has been suggested as having a role in the pathogenesis of some diseases. Metabolic syndrome (MS) is significantly associated with cardiovascular disease and type 2 diabetes. The pathogenesis of MS is complex and not well understood. The purposes of the present study were to compare enzymatic and non-enzyme antioxidants, anthropometric, hematological, and biochemical findings between subjects with MS and without MS and to evaluate the relationship between antioxidant status and hematological parameters with the components of MS.. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. Three hundred Thais, 124 with MS and 176 without MS, were included in the study. Each subject was tested for erythrocyte superoxide dismutase (SOD), glutathione peroxidase, (GPX), catalase (CAT), albumin and vitamin C levels, and hematological findings.. Subjects with MS had lower SOD and CAT levels than those without MS (p < 0.01). Subjects with MS had lower vitamin C and albumin levels than those without MS (p < 0.05). The hematological findings were not significantly different between those with and without MS except the white blood cell (WBC) count which was significantly higher in those with MS. SOD and CAT levels were significantly positively associated with HDL-C levels and negatively associated with components of MS. After adjusting for potential covariates, we found lower SOD and vitamin C levels and higher WBC counts were significantly associated with MS (p < 0.05).. These findings suggest an alteration in antioxidant status and an increase in inflammatory markers are associated with MS and its components among Thais; subjects with MS may be more likely to have oxidative stress problems.

Topics: Adult; Anthropometry; Antioxidants; Ascorbic Acid; Biomarkers; Catalase; Female; Glutathione Peroxidase; Humans; Inflammation; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Superoxide Dismutase; Thailand

Vitamin C (l-ascorbic acid, VC) and vitamin E (α-tocopherol, VE) play important physiological roles as endogenous antioxidants in many tissues and organs. However, their roles in the brain remain entirely elusive. We established senescence marker protein 30 (SMP30)/α-tocopherol transfer protein (αTTP) double knockout (DKO) mice as a novel VC and VE double-deficiency model and examined the effect of VC and VE double-deficiency on brain functions.. DKO and wild-type (WT) mice were divided into the following two groups: mice in the CE (+) group were supplied with sufficient amounts of VC and VE and mice in the CE (-) group were deficient in both VC and VE. After 8 weeks of CE (+) or CE (-) treatments, a battery of behavioral experiments was conducted to analyze cognitive functions, including memory, through the Morris water maze and Pavlovian fear conditioning tasks.. The plasma VC and VE levels in DKO-CE (-) mice and VE level in WT-CE (-) mice were almost completely depleted after 8 weeks of the deficient treatment. The behavioral study revealed that the general behaviors, including locomotor activity and anxiety level, were not influenced by the CE (-) treatment in DKO and WT mice. However, in the Pavlovian fear conditioning task, DKO-CE (-) mice showed impaired conditioned fear memory compared with that of DKO-CE (+) mice. Furthermore, increased mRNA expression was observed in inflammatory-related genes, such as IL-6, TNFα, F4/80, and Mcp-1, in the hippocampus of DKO-CE (-) mice.. The findings of this study provide evidence that VC and VE deficiency led to impaired conditioned fear memory possibly caused by neuroinflammation in the brain.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Calcium-Binding Proteins; Carrier Proteins; Conditioning, Classical; Fear; Inflammation; Intracellular Signaling Peptides and Proteins; Maze Learning; Memory; Mice; Mice, Knockout; Vitamin E; Vitamin E Deficiency

Intestinal multidrug resistance-associated protein 2 is an ABC transporter that limits the absorption of xenobiotics ingested orally, thus acting as essential component of the intestinal biochemical barrier. Metabolic Syndrome (MetS) is a pathological condition characterized by dyslipidemia, hyperinsulinemia, insulin resistance, chronic inflammation, and oxidative stress (OS). In a previous study we demonstrated that MetS-like conditions induced by fructose in drinking water (10% v/v, during 21 days), significantly reduced the expression and activity of intestinal Mrp2 in rats. We here evaluated the potential beneficial effect of geraniol or vitamin C supplementation, natural compounds with anti-inflammatory and anti-oxidant properties, in reverse fructose-induced Mrp2 alterations. After MetS-like conditions were induced (21 days), animals were cotreated with geraniol or vitamin C or vehicle for another 14 days. Decreased expression of Mrp2 protein and mRNA due to fructose administration was reversed by geraniol and by vitamin C, consistent with restoration of Mrp2 activity evaluated in everted intestinal sacs. Concomitantly, increased intestinal IL-1β and IL-6 levels induced by fructose were totally and partially counterbalanced, respectively, by geraniol administration. The intestinal redox unbalance generated by fructose was improved by geraniol and vitamin C, as evidenced by decreasing lipid peroxidation products and activity of Superoxide Dismutase and by normalizing glutathione reduced/oxidized glutathione ratio. The restoration effects exhibited by geraniol and vitamin C suggest that local inflammatory response and OS generated under MetS-like conditions represent important mediators of the intestinal Mrp2 down-regulation. Additionally, both agents could be considered of potential therapeutic value to preserve Mrp2 function under MetS conditions.

Topics: Acyclic Monoterpenes; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; ATP-Binding Cassette Transporters; Body Weight; Down-Regulation; Eating; Fructose; Glucose; Inflammation; Insulin Resistance; Intestinal Mucosa; Male; Oxidative Stress; Rats, Wistar; Triglycerides

We have previously shown that ascorbic acid (AsA) deficiency elevates hepatic expression of acute phase proteins (APPs), inflammatory markers, in Osteogenic Disorder Shionogi (ODS) rats, which are unable to synthesize AsA. However, the precise mechanisms of this elevation are unknown. Signal transducer and activator of transcription 3 (STAT3) is one of the transcription factors inducing the expression of APPs and is activated by several cytokines including interleukin-6 (IL-6). The aim of this study was to determine whether AsA deficiency stimulates hepatic STAT3 activation and increases intestinal production of proinflammatory cytokines such as IL-6. Male ODS rats (6 weeks old) were fed either a basal diet containing 300 mg AsA/kg (control group) or an AsA-free diet (AsA-deficient group) for 18 days. AsA deficiency gradually and simultaneously elevated both mRNA levels of APPs (haptoglobin, α1-acid glycoprotein, C-reactive protein and α2-macroglobulin) and nuclear level of phosphorylated STAT3 (activated STAT3) in the liver. These results showed that the AsA-deficiency-induced expression of hepatic APPs is stimulated by proinflammatory cytokines activating STAT3. On day 14, AsA deficiency significantly elevated IL-6 mRNA level in the ileum and the concentration of IL-6 in portal blood. Furthermore, the portal concentration of IL-6 positively correlated with hepatic mRNA levels of STAT3-regulated genes. These findings suggest that IL-6, produced in the intestine as a result of AsA deficiency, is recruited to the liver via the portal vein and contributes to hepatic STAT3 activation and the elevated expression of APPs.

Topics: Acute-Phase Proteins; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Nucleus; Cytosol; Duodenum; Gene Expression Profiling; Inflammation; Interleukin-6; Liver; Male; Osteogenesis; Phosphorylation; Rats; STAT3 Transcription Factor

The phytochemical composition and the antioxidant and anti-inflammatory activities of a mixture of 23 plants, named Horchata, traditionally consumed in Ecuador, have been evaluated. The study was carried out using the hydroalcoholic extract (HHext) and infusion (IHext) of the horchata plant mixture. It was verified that thermal treatment affected the contents of vitamin C and carotenoids, but hardly those of polyphenols, which would be the main bioactive compounds in the infusion, the common form of preparation of horchata for consumption. Among phenolic compounds, caffeoylquinic acids, flavones and flavonols (mostly quercetin glycosides) were prominent. Both HHext and IHext extracts managed to protect RAW 264.7 macrophages against LPS-induced cytotoxic damage, increasing the levels of endogenous antioxidant enzymes and modulating the production of pro-inflammatory and anti-inflammatory cytokines. Greater protective effects were obtained for HHext compared to IHext, which was in agreement with its higher content of phenolic compounds favoured by a more efficient extraction in the hydroalcoholic medium. Nonetheless, the infusion still maintained a significant antioxidant and anti-inflammatory activity, which would support the protective effects on health traditionally attributed to its consumption by the population.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Biomarkers; Carotenoids; Ecuador; Inflammation; Interleukin-10; Interleukin-6; Lipopolysaccharides; Mice; Nitrites; Oxidative Stress; Plant Extracts; Plants, Medicinal; Polyphenols; RAW 264.7 Cells; Temperature; Tumor Necrosis Factor-alpha

Human 5-Lipoxygenase (5-LOX) is a key enzyme targeted for asthma and inflammation. Zileuton, the only drug against 5-LOX, was withdrawn from the market due to several problems. In the present study, the performance of rationally designed conjugates of thiazole (2) and thiourea (3) scaffolds from our previously reported 2-amino-4-aryl thiazole (1) is reported. They are synthesized (total 31 derivatives), characterized, and tested against the 5-LOX enzyme in vitro and the mode of action of the most active ones are determined. Compound 2m exhibited an IC

Topics: Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Drug Design; Humans; Inflammation; Lipoxygenase Inhibitors; Molecular Docking Simulation; Structure-Activity Relationship; Thiazoles

Alarming increase of death due to S. aureus sepsis demands newer treatment strategies. Enhancement of antibiotic resistant S. aureus strains caused increased mortality. Only antibiotic treatment for Staphylococcal sepsis has been found insufficient to improve outcomes. In the innate immune response, phagocytosis mediated killing of pathogen and further triggering of intracellular signaling cascades by the PRRs culminates in the release of a variety of pro inflammatory cytokines, which orchestrate together in the early host response to infection. Increased production of inflammatory cytokines not only delineate pathogen burden but also affects host cell by triggering inflammation. Therefore, combinational therapy of Ascorbic acid is used along with antibiotics Ofloxacin (OFX) or Chloramphenicol (CHL) to kill S. aureus by mouse peritoneal macrophages. For this ROS like H

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Chloramphenicol; Cyclooxygenase 2; Cytokines; Drug Therapy, Combination; Hydrogen Peroxide; Inflammation; Macrophages, Peritoneal; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Nitric Oxide; Ofloxacin; Phagocytosis; Staphylococcal Infections; Superoxides; Toll-Like Receptor 2

Critically ill polytrauma patients have increased production of free radicals (FRs) and consequent alterations in biochemical pathways, as well as disruption of cellular integrity, due to increased lipid peroxidation. The aim of this study was to investigate several biomarkers associated with increased oxidative stress in critically ill polytrauma patients, and to evaluate the effect of antioxidant treatment on the clinical outcome in these patients. A total of 67 polytrauma patients from an intensive care unit met the selection criteria. Antiox group included 35/67 patients who received antioxidant therapy, while 32/67 patients without antioxidant treatment were considered as control group. Antioxidant therapy consisted of simultaneous administration of Vitamin C (sodium ascorbate) and N-acetylcysteine, through continuous intravenous infusion. Clinical and paraclinical evaluation of the patients was performed daily until discharge or death. At admission, laboratory parameters did not differ significantly between two groups. At discharge/upon death, statistically significant differences in favor of Antiox group were observed in the following parameters: thrombocytes, activated partial thromboplastin time, prothrombin time, total bilirubin, total cholesterol, high-density lipoproteins, low-density lipoproteins, erythrocyte sedimentation rate, interleukin 6 (all p = 0.0001), total protein (p = 0.0005), serum albumin (p = 0.0004), lactate dehydrogenase (p = 0.0006), and C-reactive protein (p = 0.0014). Starting from day 5, the APACHE II score was significantly decreased in Antiox versus control group (p < 0.05). Finally, the sepsis incidence and mortality rate were significantly lower in Antiox group (p < 0.05). Decreasing the level of oxidative stress by antioxidant substances significantly correlated with a better prognosis and outcome in our patients. Further studies should elucidate more clearly the mechanism of action of antioxidants in critically ill polytrauma patients.

Topics: Acetylcysteine; Adult; Antioxidants; APACHE; Ascorbic Acid; Biomarkers; Critical Care; Critical Illness; Female; Humans; Inflammation; Lipid Peroxidation; Lipids; Male; Middle Aged; Multiple Trauma; Oxidative Stress; Partial Thromboplastin Time; Prospective Studies; Sepsis; Treatment Outcome

Topics: Animals; Apoptosis; Ascorbic Acid; Cadmium; Catalase; DNA Damage; Erythrocytes; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Heart; Inflammation; Male; Myocardium; Rats, Wistar

Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the proinflammatory and procoagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of multiple injuries and hemorrhage.. Male Sinclair swine (n = 24; mean body weight, 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiologic monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500 mL of hydroxyethyl starch, and randomized to receive either intravenous normal saline (NS), low-dose VitC (50 mg/kg; LO), or high-dose VitC (200 mg/kg; HI). Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours postresuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung.. Compared with VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue proinflammatory mediators (IL-1β, IL-8, TNFα), plasminogen activation inhibitor-1 and tissue factor. There were no statistically significant differences between treatment groups on mean arterial pressure or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours.. Although correction of coagulation dysfunction was modest, intravenous high-dose VitC may mitigate the proinflammatory/procoagulant response that contributes to multiple organ failure following acute severe multiple injuries.. Prospective randomized controlled blinded trial study, Preclinical (animal-based).

Topics: Animals; Anti-Inflammatory Agents; Anticoagulants; Ascorbic Acid; Blood Coagulation Disorders; Disease Models, Animal; Inflammation; Male; Multiple Trauma; Random Allocation; Resuscitation; Shock, Hemorrhagic; Swine

A rat model of multifidus muscles injury and atrophy after posterior lumbar spine surgery.. We determined the effect of ascorbic acid (AA) on the postoperative multifidus muscles in rat model.. Previous studies show oxidative stress and inflammation are two main molecular mechanisms in multifidus muscle injury and atrophy after posterior lumbar surgery. AA may have a protective effect in postoperative multifidus muscles.. Rats were divided into sham surgery, control surgery, and surgery plus AA groups. Multifidus muscles of the control and AA groups were excised from the osseous structures. The muscles were retracted continuously for 2 hours. In the sham and AA groups, AA was administered via oral gavage daily in the first week. In each group, the oxidative stress was evaluated by measuring malondialdehyde (MDA) and Total superoxide dismutase (T-SOD). The inflammation, fat degeneration, or fibrosis of multifidus muscle were evaluated by quantitative real-time polymerase chain reaction (q-PCR), histology, or immunohistochemical analysis.. T-SOD activity was significantly lower in the control group than that in the AA group in the first week. MDA levels were significantly higher in the AA group. Interleukin-6 and tumor necrosis factor-α in multifidus muscles also showed significant differences when treated with AA. The inflammation score on histology was significantly lower in the AA group postoperatively in the first week. In the long run, marker genes for fibrosis and fat degeneration, and fibrosis and fat degeneration scores, were significantly lower in the AA than the control group on days 14 and 28 postoperatively.. In conclusion, AA attenuated the oxidative stress and inflammation response in the postoperative multifidus muscles, and remarkable differences were observed from the histological assessment and related marker genes expression. Our results provided important insight into the anti-inflammatory and anti-oxidative effects of AA in the postoperative multifidus muscles.. N/A.

Topics: Adipose Tissue; Animals; Antioxidants; Ascorbic Acid; Fibrosis; Inflammation; Interleukin-6; Lumbar Vertebrae; Male; Malondialdehyde; Muscular Atrophy; Neurosurgical Procedures; Orthopedic Procedures; Oxidative Stress; Paraspinal Muscles; Rats; Superoxide Dismutase; Tumor Necrosis Factor-alpha

To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1β in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1β levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1β concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1β levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1β and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.

Topics: Administration, Intravenous; Animals; Ascorbic Acid; Cytokines; Heme Oxygenase (Decyclizing); Inflammation; Kidney; Male; NF-kappa B; Oxidative Stress; Rats, Sprague-Dawley; Renal Insufficiency; Shock, Hemorrhagic; Sirtuin 1; Up-Regulation

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Body Weight; Carnitine; Cell Count; Cisplatin; Cytokines; Feeding Behavior; Gastric Mucosa; Hydrogen Peroxide; Inflammation; Inflammation Mediators; Male; Malondialdehyde; Mucus; Nitric Oxide Synthase; Oxidants; Peroxidase; Rats, Wistar

Trypanosoma cruzi infection stimulates inflammatory mediators which cause oxidative stress, and the use of antioxidants can minimize the sequelae of Chagas disease. In order to evaluate the efficacy of vitamin C in minimizing oxidative damage in Chagas disease, we orally administered ascorbic acid to Swiss mice infected with 5.0 × 10

Topics: Acute Disease; Animals; Antioxidants; Ascorbic Acid; Bilirubin; Chagas Disease; Chronic Disease; Disease Models, Animal; Inflammation; Iron; Male; Mice; Nitric Oxide; Oxidative Stress; Parasitemia; Peroxynitrous Acid; Trypanosoma cruzi

Enhanced DNA damage and disturbances in DNA repair mechanisms are reported to be involved in the pathogenesis of chronic diseases like obesity, atherosclerosis, metabolic syndrome, diabetes, and cancer. The aim of the present study was to evaluate whether anthropometric factors and dietary habits are related to endogenous DNA damage. One hundred and fourteen premenopausal, apparently healthy women were included in the study: 88 obese individuals and 26 controls. The comet assay was used to measure basal DNA damage. Biochemical measurements included lipids, apolipoproteinAI, fasting insulin, glucose, and C-reactive protein high sensitivity (CRP-hs). Dietary intakes were assessed by 3-day food records. The mean level of DNA damage was almost two times higher in obese than in non-obese women (

Topics: Adult; Anthropometry; Apolipoprotein A-I; Ascorbic Acid; Blood Glucose; C-Reactive Protein; Case-Control Studies; Cholesterol; Chronic Disease; Diet; DNA Damage; Female; Humans; Incidence; Inflammation; Insulin; Middle Aged; Nutrition Assessment; Obesity; Triglycerides; Vitamin E; Young Adult

Wound healing is an orderly complex process involving inflammation, clotting, re-epithelialization, neovascularization and wound closure. In diabetic patients, such process is impaired and delayed, posing negative economic as well as social consequences. Diabetex, (patency# EP 0877617 A1) composed of L-alanine, d-ribose, nicotinic acid and calcium ascorbate, which was initially introduced to treat cancer is thought to have anti- diabetic effects. The present study was designed to investigate the therapeutic merit of diabetex as well as the cellular mechanisms involved in such effects and its safety profile compared to metformin in wounded diabetic rats.. Sixty adult male Sprague-Dawley albino rats were randomly divided into two major groups after induction of full thickness wound; control and treated groups. Liver and kidney function test, as well as cytokines (VEGF, TGF-β, PDGF and MMP2), fasting blood sugar were measured in animal sera. Histopathological studies including hematoxyline and eosin, Masson's trichrome stains were performed on wounded tissue.. Diabetex significantly improved wound healing, collagen formation, induced re-epithelialization and neovascularization. Moreover, cytokines involved in wound healing process were increased by the antidiabetic medication. Noteworthy, the drug exhibited a safe profile on liver and kidney function tests and significantly reduced fasting blood sugar.. The present study offers a novel approach for treating diabetic resistant wounds with a possible more economic, safe strategy.

Topics: Alanine; Animals; Ascorbic Acid; Blood Coagulation; Blood Glucose; Collagen; Diabetes Mellitus, Experimental; Drug Combinations; Inflammation; Male; Matrix Metalloproteinase 2; Neovascularization, Physiologic; Niacin; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Ribose; Skin; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Wound Healing

Topics: Animals; Antioxidants; Ascorbic Acid; Chagas Disease; Drug Therapy, Combination; Inflammation; Lipid Peroxidation; Male; Mice; Nitroimidazoles; Oxidation-Reduction; Reactive Oxygen Species; Trypanocidal Agents; Trypanosoma cruzi

Topics: Antioxidants; Ascorbic Acid; Critical Care; Dose-Response Relationship, Drug; Humans; Inflammation; Infusions, Parenteral

We investigated the role of oxidative stress and the inflammasome in trauma-induced axon degeneration and vision loss using a mouse model. The left eyes of male mice were exposed to over-pressure air waves. Wild-type C57Bl/6 mice were fed normal, high-vitamin-E (VitE), ketogenic or ketogenic-control diets. Mice lacking the ability to produce vitamin C (VitC) were maintained on a low-VitC diet. Visual evoked potentials (VEPs) and retinal superoxide levels were measured in vivo. Tissue was collected for biochemical and histological analysis. Injury increased retinal superoxide, decreased SOD2, and increased cleaved caspase-1, IL-1α, IL-1β, and IL-18 levels. Low-VitC exacerbated the changes and the high-VitE diet mitigated them, suggesting that oxidative stress led to the increase in IL-1α and activation of the inflammasome. The injury caused loss of nearly 50% of optic nerve axons at 2 weeks and astrocyte hypertrophy in mice on normal diet, both of which were prevented by the high-VitE diet. The VEP amplitude was decreased after injury in both control-diet and low-VitC mice, but not in the high-VitE-diet mice. The ketogenic diet also prevented the increase in superoxide levels and IL-1α, but had no effect on IL-1β. Despite this, the ketogenic diet preserved optic nerve axons, prevented astrocyte hypertrophy, and preserved the VEP amplitude. These data suggest that oxidative stress induces priming and activation of the inflammasome pathway after neurotrauma of the visual system. Further, blocking the activation of the inflammasome pathway may be an effective post-injury intervention.

Topics: Animals; Antioxidants; Ascorbic Acid; Axons; Diet, Ketogenic; Disease Models, Animal; Evoked Potentials, Visual; Inflammasomes; Inflammation; Interleukin-1alpha; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Optic Nerve Injuries; Oxidative Stress; Reactive Oxygen Species; Retina; Superoxides; Vitamin E

The aim of this study was to verify the protective effects of ascorbic acid (AsA) against lipopolysaccharide (LPS)-induced sepsis. The study was conducted using osteogenic disorder Shionogi (ODS) rats, which are unable to synthesize AsA. Male ODS rats (6 wk old) were fed either an AsA-free diet (AsA-deficient group), a diet supplemented with 300 mg/kg AsA (control group), or a diet supplemented with 3,000 mg/kg AsA (high-AsA group) for 8 d. On day 8, all the rats were intraperitoneally injected with LPS (15 mg/kg body weight). Forty-eight hours after the injection, the survival rates of the rats in the control (39%) and the high-AsA (61%) groups were significantly higher than that in the AsA-deficient group (5.5%). Next, we measured several inflammatory parameters during 10 h after administering LPS. At 6 h, elevated serum levels of markers for hepatic and systemic injuries were suppressed in rats fed AsA. Similarly, 10 h after LPS injection, the elevation in the serum levels of markers for renal injury were also suppressed proportionally to the amount of AsA in the diet. The elevated serum concentrations of TNFα and IL-1β by LPS in the AsA-deficient group decreased in groups fed AsA. Hematic TNFα mRNA levels at 6 h after the LPS injection were also lowered by feeding AsA. These results demonstrated that the dietary intake of AsA improved the survival rates and suppressed the inflammatory damage, in a dose-dependent manner, caused during sepsis induced by LPS in ODS rats.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Supplements; Inflammation; Interleukin-1beta; Kidney; Kidney Diseases; Lipopolysaccharides; Liver; Liver Diseases; Male; Nutritional Status; Osteogenesis; Rats; Rats, Inbred Strains; Sepsis; Tumor Necrosis Factor-alpha; Vitamins

There is increasing evidence that the plasma concentration of vitamin D, carotenoids, zinc and selenium are associated with the magnitude of the systemic inflammatory response. In order to examine whether other vitamins may be affected and whether red cell concentrations are less affected by systemic inflammation the aim of the present study was to examine the effect of the systemic inflammatory response on red cell measurements of vitamins B1, B2 and B6, and plasma concentration of vitamin C and E in a large cohort of patients referred for a nutritional screen.. Patients referred for nutritional assessment of B1 (n = 551), B2 (n = 251), B6 (n = 313), ascorbic acid (n = 494) and α-tocopherol (n = 395) concentrations. These vitamins were measured using routine laboratory methods.. The median concentrations of vitamin B1 grouped according to C-reactive protein concentrations ≤10, 11-80 and >80 mg/L were 543, 664 and 766 ng/g Hb respectively (p < 0.001, 41% higher). The median concentration of vitamin B1 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 547, 664 and 701 ng/g Hb respectively (p < 0.001, 28% higher). The median concentrations of red cell vitamin B2 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 2.2, 2.3 and 2.4 nmol/g Hb respectively (p < 0.001, 9% higher). The median red cell concentrations of vitamin B2 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 2.1, 2.4 and 2.3 nmol/g Hb respectively (p < 0.001, 14% higher). The median concentrations of red cell vitamin B6 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 534, 548 and 767 pmol/g Hb respectively (p < 0.001, 44% higher). The median red cell concentrations of vitamin B6 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 462, 644 and 840 pmol/g Hb respectively (p < 0.001, 82% higher). In contrast, the median plasma concentrations of ascorbic acid grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 25.0, 15.0 and 6.0 μmol/l respectively (78% lower, p < 0.001). The median plasma concentrations of ascorbic acid grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 32.0, 13.0 and 5.0 μmol/l respectively (84% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 5.9, 4.6 and 2.1 μmol/l respectively (64% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 6.0, 5.5 and 2.1 μmol/l respectively (65% lower, p < 0.001).. Red cell concentrations of vitamins B1, B2 and B6 were not lower with an increasing systemic inflammatory response. In contrast, plasma concentrations of vitamin C and E were lower. Therefore, compared with plasma concentration, red cell concentrations of B1, B2 and B6 are likely to be more reliable measures of status in the presence of a systemic inflammatory response.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; Erythrocytes; Female; Humans; Inflammation; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Predictive Value of Tests; Reproducibility of Results; Riboflavin; Thiamine; Vitamin B 6; Vitamin E; Young Adult

Topics: Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Antioxidants; Ascorbic Acid; Bone and Bones; Disease Progression; Fatty Acids, Omega-3; Humans; Immune System; Inflammation; Models, Theoretical; Porphyromonas gingivalis; Risk Factors; Vitamin D

Vitamin C may reduce inflammation and is inversely associated with mortality in the general population. We investigated the association of plasma vitamin C with all-cause mortality in renal transplant recipients (RTR); and whether this association would be mediated by inflammatory biomarkers. Vitamin C, high sensitive C-reactive protein (hs-CRP), soluble intercellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured in a cohort of 598 RTR. Cox regression analyses were used to analyze the association between vitamin C depletion (≤28 µmol/L; 22% of RTR) and mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. At a median follow-up of 7.0 (6.2-7.5) years, 131 (21%) patients died. Vitamin C depletion was univariately associated with almost two-fold higher risk of mortality (Hazard ratio (HR) 1.95; 95% confidence interval (95%CI) 1.35-2.81,

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Creatinine; Dietary Supplements; Endpoint Determination; Female; Follow-Up Studies; Humans; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Proteinuria; Vascular Cell Adhesion Molecule-1

Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.. Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.. The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.. Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Topics: Acetaminophen; Analgesics; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cytokines; Dinoprost; Inflammation; Interleukin-1beta; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Platelet Activation; Rats; Rats, Wistar; Thromboxane B2; Tumor Necrosis Factor-alpha

Exposure to zinc oxide nanoparticles (ZnO NPs) promotes acute pulmonary toxicity through oxidative stress and inflammation. Furthermore, dissolved zinc from ZnO NPs induces the formation of intracellular reactive oxygen species (ROS). We previously reported that supplemental ascorbic acid (AA) inhibits ZnO NP-induced acute pulmonary toxicity in a rat model; however, the mechanism of this action remains unclear. Therefore, we investigated the effects of AA on ZnO NP-induced cytotoxicity in human lung carcinoma A549 cells. AA was found to suppress intracellular production of ROS, and thus reduce the subsequent inflammation of ZnO NPs. However, intracellular Zn

Topics: A549 Cells; Antioxidants; Ascorbic Acid; Humans; Inflammation; Metal Nanoparticles; Oxidative Stress; Particle Size; Reactive Oxygen Species; Zinc Oxide

Chronic inflammation, possibly exacerbated by cigarette smoking, is considered to be the primary cause of pulmonary damage in patients with tuberculosis (TB). However, the mechanisms which underpin these harmful inflammatory responses, have not been well documented.. The current study was undertaken to determine possible associations between systemic biomarkers of inflammation (acute phase reactants, stress hormones, leukocyte vitamin C) and smoking status in patients (n=71, 20 smokers) with newly-diagnosed pulmonary TB presenting at a tertiary hospital, Johannesburg, South Africa.. Plasma concentrations of C-reactive protein (CRP), ferritin, cortisol, epinephrine, norepinephrine, dopamine and leukocyte vitamin C were measured using a combination of immunonephelometric, radioimmunoassay, immunochromatographic and spectrophotometric procedures. Demographic, clinical and laboratory data was captured and analysed by parametric and non-parametric analyses where appropriate.. Smokers were predominantly males (P<0.0001), of older age (P<0.0003) with a significantly lower body mass index (P<0.03). Plasma levels of CRP, ferritin and dopamine were higher in the group of smokers in the setting of lower levels of epinephrine, and leukocyte vitamin C, with CRP and vitamin C attaining statistical significance (P<0.04 and P<0.02 respectively). Those of cortisol and norepinephrine were comparable to those of non-smokers, as were radiographic changes and clinical indices of disease activity.. Cigarette smoking is associated with an exaggerated systemic inflammatory response in pulmonary TB in the setting of decreased concentrations of leukocyte vitamin C. Although no significant associations with radiographic changes and most clinical indices of disease activity were evident on presentation, these pro-inflammatory interactions may have prognostic significance.

Topics: Adult; Ascorbic Acid; Biomarkers; C-Reactive Protein; Dopamine; Epinephrine; Female; Ferritins; Humans; Hydrocortisone; Inflammation; Leukocytes; Male; Middle Aged; Norepinephrine; Smoking; South Africa; Tuberculosis, Pulmonary

The bone marrow (BM) plays a key role in the long-term maintenance of immunological memory. However, the impact of aging on the production of survival factors for effector/memory T cells and plasma cells in the human BM has not been studied. We now show that the expression of molecules involved in the maintenance of immunological memory in the human BM changes with age. While IL-15, which protects potentially harmful CD8

Topics: Acetylcysteine; Aging; Animals; Ascorbic Acid; Bone Marrow Cells; CD8-Positive T-Lymphocytes; Cell Survival; Cells, Cultured; Cytokines; Free Radical Scavengers; Humans; Immunologic Memory; Immunosenescence; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Reactive Oxygen Species; Superoxide Dismutase-1

The biosynthesis of leukotrienes in one of the arachidonic acid pathways and PGE

Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cytokines; Dinoprostone; Free Radicals; Gene Expression Regulation, Enzymologic; HeLa Cells; Humans; Inflammation; Isocoumarins; Kinetics; Leukotrienes; Lipoxygenase Inhibitors; Prostaglandins; RNA, Messenger

Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.

Topics: Animals; Antioxidants; Ascorbic Acid; Fibroblasts; Humans; Inflammation; Mice; Wound Healing

Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2'-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms.

Topics: Agaricales; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Bromates; Deoxyguanosine; DNA; Ergothioneine; Glutathione; Halogenation; Hypochlorous Acid; Inflammation; Male; Mice; Mice, Hairless; Peroxidase; Ultraviolet Rays

This study investigated the effect of rebamipide on activation of the NLRP3 inflammasome and generation of reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1β (IL-1β) production. Human monocyte cell line THP-1 and human umbilical venous endothelial cells (HUVECs) were used to assess the inflammatory response to MSU crystals. NADP/NADPH activity assays were used as a marker of ROS generation. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate levels of IL-1β, caspase-1, NLRP3, associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p65, IκBα, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid. In THP-1 cells, treatment with MSU crystals increased NADP/NADPH ratios and IL-1β expression, and both of these responses were potently inhibited by addition of rebamipide. Rebamipide also attenuated enhanced expression of caspase-1 gene by MSU crystals (p < 0.05). Western blotting demonstrated that MSU crystals stimulated caspase-1 but not NLRP3 and ASC activation. Similarly, MSU crystals activated the NF-κB pathway, which in turn was blocked by rebamipide. Stimulation of HUVECs with MSU crystals increased expression of VCAM-1 and ICAM-1, which were markedly inhibited by both rebamipide and dexamethasone. This study demonstrated that rebamipide inhibits IL-1β activation through suppression of ROS-mediated NF-κB signaling pathways and caspase-1 activation in MSU crystal-induced inflammation.

Topics: Alanine; Ascorbic Acid; Caspase 1; Cell Line; Colchicine; Dexamethasone; Enzyme Activation; Gout; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; NAD; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Quinolones; Reactive Oxygen Species; Signal Transduction; Uric Acid; Vascular Cell Adhesion Molecule-1

Endosulfan, a chlorinated hydrocarbon insecticide/acaricide, is a member of a cyclodiene sub-group of poisons to a wide variety of insects and mites. It is also toxic to humans and animals, but there is limited knowledge about endosulfan-related splenic and overall immunotoxicity. The aim of this study was to review pathological findings of endosulfan toxicity in the spleen and to examine potential protective effects of the anti-oxidant Vitamin C (Vit C). Here, after 6-week exposures, the spleens of New Zealand White rabbits were examined grossly and histopathologically and tissue caspase-3 activity was assessed immunohistochemically. Rabbits in four groups were used: Group END were given by oral gavage a sub-lethal dose of endosulfan (1 mg/kg) in corn oil daily for 6 weeks; Group END + C received the same dose of endosulfan daily and Vit C (20 mg/kg) every other day by gavage during this period; Group Vit C received oral corn oil daily and 20 mg/kg Vit C every other day; and Group OIL received corn oil daily for 6 weeks. Analyses of the tissues collected 1 week after the final dosing revealed lymphocyte depletion and necrosis in spleens of the hosts that received the pesticide (END only and END + C); hemorrhage and slight neutrophilic infiltration was also noted. Caspase-3 immunoreactivity was marked in lymphocytes in all spleens of rabbits in both END groups. Overall, these toxicities were mitigated by Vit C co-treatment; in END + C hosts, markedly decreased depletion of lymphocytes, inflammation and caspase-3 immunoreactivity were observed. However, even with mitigation, the level of toxicity present was still greater than any seen in the spleens of hosts that received OIL or Vit C alone. These results revealed endosulfan could cause toxicity in the rabbit spleen, characterized by depletion of lymphocytes, inflammation, necrosis and hemorrhage, and that this toxicity could begin to be mitigated by Vit C co-treatment.

Topics: Animals; Antioxidants; Ascorbic Acid; Caspase 3; Endosulfan; Hemorrhage; Immunohistochemistry; Inflammation; Lymphocytes; Necrosis; Neutrophil Infiltration; Pesticides; Rabbits; Spleen

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Topics: Adult; Ascorbic Acid; Biomarkers; C-Reactive Protein; Catalase; Farmers; Fibrinogen; Glutathione; Hemostatics; Humans; Inflammation; Logistic Models; Male; Malondialdehyde; Middle Aged; Occupational Exposure; Oxidation-Reduction; Oxidative Stress; Pesticides; Protein Carbonylation; Prothrombin; Superoxide Dismutase; Superoxides; Surveys and Questionnaires; Vitamin E

The early recruitment of inflammatory cells to sites of bone fracture and trauma is a critical determinant in successful fracture healing. Released by infiltrating inflammatory cells, myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, whose functional involvement in bone repair has mainly been studied in the context of providing a mechanism for oxidative defense against invading microorganisms. We report here novel findings that show peroxidase enzymes have the capacity to stimulate osteoblastic cells to secrete collagen I protein and generate a mineralized extracellular matrix in vitro. Mechanistic studies conducted using cultured osteoblasts show that peroxidase enzymes stimulate collagen biosynthesis at a post-translational level in a prolyl hydroxylase-dependent manner, which does not require ascorbic acid. Our studies demonstrate that osteoblasts rapidly bind and internalize both MPO and EPO, and the catalytic activity of these peroxidase enzymes is essential to support collagen I biosynthesis and subsequent release of collagen by osteoblasts. We show that EPO is capable of regulating osteogenic gene expression and matrix mineralization in culture, suggesting that peroxidase enzymes may play an important role not only in normal bone repair, but also in the progression of pathological states where infiltrating inflammatory cells are known to deposit peroxidases.

Topics: Arthroplasty, Replacement, Hip; Ascorbic Acid; Bone and Bones; Cells, Cultured; Collagen; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Eosinophil Peroxidase; Extracellular Matrix; Female; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Heme; Humans; Inflammation; Osteoblasts; Peroxidases; Protein Processing, Post-Translational; Recombinant Proteins

The impact of ascorbate on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. Heatstroke is defined as a form of excessive hyperthermia associated with a systemic inflammatory response that results in multiple organ dysfunctions in which central nervous system disorders such as delirium, convulsions, and coma are predominant. The thermoregulatory, immune, coagulation and tissue injury responses of heatstroke closely resemble those observed during sepsis and are likely mediated by similar cellular mechanisms. This study was performed by using the characteristic high lethality rate and sepsis-mimic systemic inflammatory response of a murine model of heat stroke to test our hypothesis that supra-physiological doses of ascorbate may have therapeutic use in critical care. We demonstrated that parenteral administration of ascorbate abrogated the lethality and thermoregulatory dysfunction in murine model of heat stroke by attenuating heat stroke-induced accelerated systemic inflammatory, coagulation responses and the resultant multiple organ injury, especially in hypothalamus. Overall, our findings support the hypothesis and notion that supra-physiological doses of ascorbate may have therapeutic use in critical care.

Topics: Animals; Ascorbic Acid; Death; Heat Stroke; Humans; Hypothalamus; Inflammation; Mice; Neurons; Sepsis

Cytokines play an important role in tumor angiogenesis and inflammation. There is evidence in the literature that high doses of ascorbate can reduce inflammatory cytokine levels in cancer patients. The objective of this study was to investigate the effect of treatment by intravenous vitamin C (IVC) on cytokines and tumor markers.. With the availability of protein array kits allowing assessment of many cytokines in a single sample, we measured 174 cytokines and additional 54 proteins and tumor markers in 12 cancer patients before and after a series of IVC treatments.. Presented results show for our 12 patients the effect of treatment resulted in normalization of many cytokine levels. Cytokines that were most consistently elevated prior to treatments included M-CSF-R, Leptin, EGF, FGF-6, TNF-α, β, TARC, MCP-1,4, MIP, IL-4, 10, IL-4, and TGF-β. Cytokine levels tended to decrease during the course of treatment. These include mitogens (EGF, Fit-3 ligand, HGF, IGF-1, IL-21R) and chemo-attractants (CTAC, Eotaxin, E-selectin, Lymphotactin, MIP-1, MCP-1, TARC, SDF-1), as well as inflammation and angiogenesis factors (FGF-6, IL-1β, TGF-1).. We are able to show that average z-scores for several inflammatory and angiogenesis promoting cytokines are positive, indicating that they are higher than averages for healthy controls, and that their levels decreased over the course of treatment. In addition, serum concentrations of tumor markers decreased during the time period of IVC treatment and there were reductions in cMyc and Ras, 2 proteins implicated in being upregulated in cancer.

Topics: Adult; Antineoplastic Agents; Ascorbic Acid; Biomarkers, Tumor; Case-Control Studies; Cytokines; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Neovascularization, Pathologic; Proto-Oncogene Proteins c-myc; ras Proteins; Up-Regulation

The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans.. We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration.. Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans.. The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

Topics: Adult; Animals; Ascorbic Acid; Case-Control Studies; Double-Blind Method; Exercise; Humans; Inflammation; Male; Oxidative Stress; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Wistar; Species Specificity; Vitamins

Developing an in vitro microenvironment using cell-derived decellularized extracellular matrix (dECM) is a promising approach to efficiently expand adult stem cells for cartilage engineering and regeneration. Ascorbic acid serves as a critical stimulus for cells to synthesize collagens, which constitute the major component of dECM. In this study, we hypothesized that optimization of ascorbate treatment would maximize the rejuvenation effect of dECM on expanded stem cells from human infrapatellar fat pad in both proliferation and chondrogenic differentiation. In the duration regimen study, we found that dECM without L-ascorbic acid phosphate (AA) treatment, exhibiting lower stiffness measured by atomic force microscopy, yielded expanded cells with higher proliferation capacity but lower chondrogenic potential when compared to those with varied durations of AA treatment. dECM with 250 µM of AA treatment for 10 d had better rejuvenation in chondrogenic capacity if the deposited cells were from passage 2 rather than passage 5, despite no significant difference in matrix stiffness. In the dose regimen study, we found that dECMs deposited by varied concentrations of AA yielded expanded cells with higher proliferation capacity despite lower expression levels of stem cell related surface markers. Compared to cells expanded on tissue culture polystyrene, those on dECM exhibited greater chondrogenic potential, particularly for the dECMs with 50 µM and 250 µM of AA treatment. With the supplementation of ethyl-3,4-dihydroxybenzoate (EDHB), an inhibitor targeting procollagen synthesis, the dECM with 50 µM of AA treatment exhibited a dramatic decrease in the rejuvenation effect of expanded cell chondrogenic potential at both mRNA and protein levels despite no significant difference in matrix stiffness. Defined AA treatments during matrix preparation will benefit dECM-mediated stem cell engineering and future treatments for cartilage defects.

Topics: Adipose Tissue; Animals; Ascorbic Acid; Biomechanical Phenomena; Cartilage; Cell Differentiation; Cell Lineage; Cell Proliferation; Chondrocytes; Chondrogenesis; Collagen; Elasticity; Extracellular Matrix; Female; Humans; Inflammation; Male; Phenotype; Polystyrenes; RNA, Messenger; Stem Cells; Tissue Engineering; Young Adult

The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Colchicine; Hippocampus; Inflammation; Male; Memory; Mice; Oxidative Stress; Rats; Reactive Oxygen Species; Vitamins

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Prenatal exposure to lipopolysaccharide (LPS) leads to hypertension in a rat offspring. However, the mechanism is still unclear. This study unraveled epigenetic mechanism for this and explored the protective effects of ascorbic acid against hypertension on prenatal inflammation-induced offspring. Prenatal LPS exposure resulted in an increase of intrarenal oxidative stress and enhanced angiotensin-converting enzyme 1 (ACE1) gene expression at the mRNA and protein levels in 6- and 12-week-old offspring, correlating with the augmentation of histone H3 acetylation (H3AC) on the ACE1 promoter. However, the prenatal ascorbic acid treatment decreased the LPS-induced expression of ACE1, protected against intrarenal oxidative stress, and reversed the altered histone modification on the ACE1 promoter, showing the protective effect in offspring of prenatal LPS stimulation. Our study demonstrates that ascorbic acid is able to prevent hypertension in offspring from prenatal inflammation exposure. Thus, ascorbic acid can be a new approach towards the prevention of fetal programming hypertension.

Topics: Acetylation; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Body Weight; CpG Islands; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Histones; Hypertension; Inflammation; Kidney; Lipopolysaccharides; Oxidative Stress; Peptidyl-Dipeptidase A; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Risk Factors; RNA, Messenger

One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables.. This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death.. Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865).. Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

Topics: Abbreviated Injury Scale; Acetylcysteine; Adult; Aged; Antioxidants; Ascorbic Acid; Critical Illness; Female; Humans; Incidence; Inflammation; Injury Severity Score; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Oxidation-Reduction; Oxidative Stress; Respiration, Artificial; Retrospective Studies; Sepsis; Thiamine; Thoracic Injuries

We have previously shown that quercetin modulates the proinflammatory effect of β-carotene (BC) induced by oral benzo[a]pyren (Bap) partly through the regulation of the JNK pathway. In the present study, we determined whether the combination of BC and quercetin regulates the antioxidant enzymes and the activation of NF-κB in Mongolian gerbils exposed to Bap. We also compared the combined effects of BC+ quercetin with that of BC+ ascorbic acid (C)+ α-tocopherol (E).. The gerbils were given BC (10 mg/kg) alone or in combination with quercetin (50 or 100 mg/kg) or C (13 mg/kg)+E (92 mg/kg) by gavage 3 times/week for 6 months. During the first 2 months, the gerbils were exposed to Bap by intratracheal instillation once/week. The levels of proinflammatory cytokines, thiobarbituric acid reactive substances, antioxidant enzymes and NF-κB activation in the plasma or the lungs were determined.. Bap increased the level of proinflammatory cytokines and oxidative stress in the plasma or lungs, while it decreased the antioxidant systems. Bap also increased nuclear NF-κB levels in the lungs. BC partly recovered the Bap-induced decrease in antioxidant activity, antioxidant enzyme activities and glutathione levels but had no effect on proinflammatory cytokines and NF-κB translocation. BC in combination with quercetin or C+E suppressed all the harmful effects induced by Bap. All the effects of quercetin at 100 mg/kg were similar to the effect of C+E.. BC in combination with quercetin or C+E rather than BC alone similarly suppresses the Bap-induced inflammatory reaction that was accompanied by the regulation of antioxidant enzymes and the translocation of NF-κB in vivo.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Benzo(a)pyrene; beta Carotene; Catalase; Gerbillinae; Glutathione; Glutathione Peroxidase; Inflammation; Interleukin-1beta; Lipid Peroxidation; Lung; Male; NF-kappa B; Oxidative Stress; Quercetin; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

Vitamin C (ascorbic acid, AA) is a water soluble vitamin with many functions including antioxidative properties, haemostasis, hormone synthesis, collagen synthesis, carnitine synthesis, bile salt production and enhancing iron absorption. There is some evidence that there is a negative inverse relationship between plasma vitamin C concentration and the systemic inflammatory response as measured by C-reactive protein (CRP). The aim of the present study was to examine, in the context of a longitudinal study, the change in plasma concentrations of ascorbic acid (AA) and Vitamin E (α-tocopherol, AT) and their relationship to free radical damage during the evolution of the systemic inflammatory response.. Venous blood samples were obtained pre-operatively and at 1, 2, 3 and 90 days post-operatively from 11 patients undergoing elective hip arthroplasty at Glasgow Royal Infirmary. AA, AT, cholesterol, MDA (marker of free radical damage), CRP and albumin were measured in plasma.. Plasma AA fell significantly by 74% (P < 0.01), AT fell by 36% (P < 0.01), cholesterol by 40% (P < 0.01), MDA by 38% (P < 0.01), albumin by 29% (P < 0.01) and CRP increased significantly by 160 fold (P < 0.01) during the systemic inflammatory response. The fall in plasma AA remained significant when adjusted for albumin (P < 0.01). Plasma AT adjusted for cholesterol did not change significantly during the study period. The fall in plasma MDA remained significant when adjusted for albumin (P 0.01). At 3 months post-operatively, all measurements (including AA) except albumin had returned to baseline values.. Plasma AA levels are unlikely to be a reliable measurement of Vitamin C where there is evidence of a systemic inflammatory response. The decrease in plasma AA concentration is likely to be secondary to increased consumption, increased usage neutralising free radicals, increased utilisation in supporting AT regeneration and increased urinary excretion.

Topics: Adult; Aged; alpha-Tocopherol; Arthroplasty; Ascorbic Acid; Biomarkers; C-Reactive Protein; Cholesterol; Female; Hip; Humans; Inflammation; Lipid Peroxidation; Longitudinal Studies; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Serum Albumin

Cigarette smoke (CS) is the strongest risk factor for emphysema. However, the mechanism of the disease is not clear. One reason is that each puff of CS is a complex mixture of approximately 4,000 chemicals, and it is yet to be known which of these chemical(s) are directly involved in the pathogenesis of lung injury in emphysema. The purpose of this study was to demonstrate that p-benzoquinone (p-BQ) produced in the lungs of CS-exposed guinea pigs is a causative factor for destruction of alveolar cells resulting in emphysema that is prevented by vitamin C. Vitamin C-restricted guinea pigs were subjected to whole-body CS exposure from five Kentucky research cigarettes (3R4F) per day or intramuscular injection of p-BQ in amounts approximately produced in the lung from CS exposure with and without oral supplementation of vitamin C. Progressive exposure of CS or p-BQ treatment caused progressive accumulation of p-BQ in the lung that was accompanied by destruction of alveolar cells and emphysema. The pathogenesis involved was arylation, oxidative stress, inflammation, and apoptosis. Vitamin C (30 mg/kg body weight/d), a potential antagonist of p-BQ, prevented accumulation of p-BQ in the lung and the pathogenesis of emphysema. Our study provides the first proof that inactivation of p-BQ, a causative factor of emphysema in CS-exposed lung, could constitute a novel and effective approach in the prevention of emphysema. We consider that a moderately high dose of vitamin C may be a simple preventive therapy for emphysema in chronic smokers.

Topics: Animals; Apoptosis; Ascorbic Acid; Benzoquinones; Disease Models, Animal; Guinea Pigs; Inflammation; Oxidative Stress; Pulmonary Alveoli; Pulmonary Emphysema; Smoke; Smoking

Current evidence supports the positive association between the consumption of plant foods and health. In this work, we assessed the effect of consuming a half-serving (30 g) or one serving (60 g) of broccoli sprouts on the urinary concentrations of biomarkers of oxidative stress (isoprostanes) and inflammation (prostaglandins and thromboxanes). Twenty-four volunteers participated in the project. A quantitative determination of sulforaphane and its mercapturic derivatives, eicosanoids, and total vitamin C in urine was performed. The intake of broccoli sprouts produced an increase in the urinary concentrations of sulforaphane metabolites and vitamin C. Among the 13 eicosanoids analyzed, tetranor-PGEM and 11β-PGF2α as well as 11-dehydro-TXB2 showed a significant decrease in their urinary concentrations after the ingestion of broccoli sprouts. Therefore, the consumption of broccoli sprouts modulated the excretion of biomarkers linked to inflammation and vascular reactions without exerting a significant influence on the oxidation of phospholipids in vivo.

Topics: Adult; Ascorbic Acid; Biomarkers; Brassica; Chromatography, High Pressure Liquid; Cross-Over Studies; Female; Glucosinolates; Healthy Volunteers; Humans; Imidoesters; Inflammation; Isoprostanes; Isothiocyanates; Male; Middle Aged; Oxidative Stress; Oximes; Plant Extracts; Prostaglandins; Sulfoxides; Tandem Mass Spectrometry; Thromboxane B2; Vascular Diseases; White People; Young Adult

This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5 and 5 µg/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret. Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cysteine; Cystine; Disulfides; Glutathione; Inflammation; Injections, Intravenous; Lipopolysaccharides; Male; Oxidative Stress; Rats; Tocopherols; Uric Acid

Recent, unexpected high failure rates of metal-on-metal hip implants have reintroduced the issue of cobalt toxicity. An adverse reaction to cobalt ions and cobalt-induced lung injury occurs during environmental exposure and is now strictly controlled. Currently adverse reaction occurs to cobalt nanoparticles during wear and tear of metal-on-metal hip implants of which the underlying mechanism is not fully understood. The putative role of the hypoxia-inducible factor (HIF) pathway in the mechanism of cobalt nanoparticle (Co-NPs) toxicity was examined using the U937 cell line, human alveolar macrophages and monocyte-derived macrophages. Co-NPs (5-20 μg/ml)-induced cytotoxicity (viability ranged from 75% to <20% of control, respectively) and reactive oxygen species (ROS), whereas a comparable concentration of cobalt ions (Co(II); up to 350 μM) did not. Co-NPs induced HIF-1α stabilization. Addition of ascorbic acid (100 µM) and glutathione (1 mM) both prevented the increased ROS. However, only treatment with ascorbic acid reduced HIF-1α levels and prevented cell death, indicating that a ROS-independent pathway is involved in Co-NPs-induced cytotoxicity. Replenishing intracellular ascorbate, which is crucial in preventing HIF pathway activation, modified Co-induced HIF target gene expression and the inflammatory response, by decreasing interleukin-1 beta (IL-1β) mRNA and protein expression. Addition of glutathione had no effect on Co-NPs-induced HIF target gene expression or inflammatory response. Thus, Co-NPs induce the HIF pathway by depleting intracellular ascorbate, leading to HIF stabilization and pathway activation. This suggests a strong, ROS-independent role for HIF activation in Co-NPs-induced cytotoxicity and a possible role for HIF in metal-on-metal hip implant pathology.

Topics: Ascorbic Acid; Cell Death; Cells, Cultured; Cobalt; Dose-Response Relationship, Drug; Glutathione; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Macrophages; Nanoparticles; Reactive Oxygen Species; Signal Transduction

Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP. We hypothesized that common resuscitation fluids such as normal saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile water (LP-SW) would yield similar inflammation profiles and DNA damage following LP reconstitution and transfusion.. This was a randomized, prospective, blinded animal study. LP was reconstituted to 50% of original volume with NS, LR, HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction (RT-PCR).. Reconstituted LP pH was similar between groups before resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated increased DNA damage at 4 hours versus baseline but also had the lowest C-reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences between groups were similar for DNA damage and lung inflammation.. Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA damage following LP transfusion in this swine polytrauma model. Based on universal availability, these data suggest that sterile water is the most logical choice for LP reconstitution in humans.. Prognostic, level II.

Topics: Animals; Antioxidants; Ascorbic Acid; C-Reactive Protein; Disease Models, Animal; DNA Damage; Female; Femoral Fractures; Fluid Therapy; Freeze Drying; Hemorrhage; Hydrogen-Ion Concentration; Inflammation; Liver; Lung; Oxidative Stress; Plasma; Prospective Studies; Random Allocation; Real-Time Polymerase Chain Reaction; Swine; Water

The aim of the present study was to examine the association between intake of five common antioxidative nutrients from supplements and medications (vitamin E, vitamin C, carotenoids, Se, and Zn) and levels of high-sensitivity C-reactive protein (hs-CRP) in the general population. For this purpose, a total of 2924 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006-8) were investigated cross-sectionally. Intake of dietary supplements and medication during the last 7 d was recorded in a personal interview, when participants were asked to show product packages of ingested preparations. Linear regression models were calculated; first, the exposure to regular nutrient intake was treated with a binary response (yes/no); then regularly ingested amounts were divided into quartiles to examine dose-response relationships. Effect of single v. combined supplementation of antioxidants was assessed through the inclusion of interaction terms into the models. Regular intake of any of the five investigated antioxidants per se was not associated with hs-CRP levels. However, dose-response analyses revealed that participants who regularly ingested more than 78 mg vitamin E/d, which corresponds to the upper quartile, had 22% lower hs-CRP levels (95% CI 0·63, 0·97) compared to those of persons who were not exposed to any vitamin E supplementation. Stratified analyses showed that this association was found only in persons who took vitamin E in combination with other antioxidants. The combined supplementation of vitamin E with other antioxidants could thus be a promising strategy for the prevention of inflammation-related diseases in the general population, if further studies could confirm that the proposed association is causal.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Inflammation; Male; Middle Aged; Motor Activity; Selenium; Vitamin E; Zinc

Although growing evidence from trials and population-based studies has supported a protective role for flavonoids in relation to risk of certain chronic diseases, the underlying mechanisms remain unclear. Several previous studies focused on individual inflammatory biomarkers, but because of the limited specificity of any individual marker, an assessment of a combination of biomarkers may be more informative.. We used an inflammation score (IS) that integrated 12 individual inflammatory biomarkers for the examination of associations with intakes of different flavonoid classes.. The study was a cross-sectional analysis of 2375 Framingham Heart Study Offspring Cohort participants. Intakes of total flavonoids and their classes (anthocyanins, flavonols, flavanones, flavan-3-ols, polymers, and flavones) were calculated from validated food-frequency questionnaires. Individual inflammatory biomarkers were ranked, standardized, and summed to derive an overall IS and subgroup scores of functionally related biomarkers.. In multivariate analyses, an inverse association between higher anthocyanin and flavonol intakes and IS was observed with a mean ± SE difference between quintile categories 5 and 1 of -1.48 ± 0.32 (P-trend ≤ 0.001) and -0.72 ± 0.33 (P-trend = 0.01), respectively. Results remained significant after additional adjustment for physical activity and vitamin C and fruit and vegetable intakes. Higher anthocyanin intake was inversely associated with all biomarker subgroups, whereas higher flavonol intake was associated only with lower cytokine and oxidative stress biomarker concentrations. In food-based analyses, higher intakes of apples and pears, red wine, and strawberries were associated with a lower IS with differences between quintiles 5 and 1 of -1.02 ± 0.43 (P = 0.006), -1.73 ± 0.39 (P < 0.001), and -0.44 ± 0.88 (P = 0.02), respectively. Although intakes of other classes were not associated with a reduction in overall IS, higher intakes of flavan-3-ols and their polymers were associated with a significant reduction in oxidative stress biomarkers.. These findings provide evidence to suggest that an anti-inflammatory effect may be a key component underlying the reduction in risk of certain chronic diseases associated with higher intakes of anthocyanins and flavonols. The Framingham Offspring Study was registered at clinicaltrials.gov as NCT00005121 (Framingham Heart Study).

Topics: Anthocyanins; Anti-Inflammatory Agents; Ascorbic Acid; Body Mass Index; Cross-Sectional Studies; Diet; Dose-Response Relationship, Drug; Energy Intake; Female; Flavanones; Flavones; Flavonols; Fruit; Humans; Inflammation; Linear Models; Male; Malus; Middle Aged; Motor Activity; Multivariate Analysis; Observational Studies as Topic; Potassium, Dietary; Pyrus; Surveys and Questionnaires; United States

Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that the whole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design.

Topics: Adjuvants, Immunologic; Animals; Antigens; Ascorbic Acid; Delayed-Action Preparations; Humans; Inflammasomes; Inflammation; Interleukins; Leukocytes; Liquid Crystals; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Ovalbumin; Toll-Like Receptor 9; Toll-Like Receptors; Vaccines

To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health.. Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey.. Nationally representative population sample from the US.. Age ≥ 20 y with sleep data; final analytical sample of n = 2,079.. N/A.. Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤ 4, 5-6, 7-8, and ≥ 9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (< 0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration- cardiometabolic health relationships were mediated by C-reactive protein (CRP), γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and -systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship.. Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Blood Pressure; C-Reactive Protein; Cardiovascular Physiological Phenomena; Carotenoids; Cross-Sectional Studies; Female; Health Surveys; Humans; Inflammation; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Nutrition Surveys; Oxidative Stress; Sex Characteristics; Sleep; Time Factors; Transglutaminases; United States; Uric Acid; Vitamin D; Waist Circumference

Periodontitis is a chronic inflammatory disease and a significant risk factor for tooth loss. Although a link between diet and periodontal health exists, the relation between diet and healing after periodontal therapy has yet to be investigated.. The objective was to determine whether higher intakes of fruits and vegetables or nutrients with antioxidant or anti-inflammatory activity are associated with greater healing, measured as reduced probing depth (PD), after scaling and root planing (SRP), a cost-effective treatment to manage periodontal disease and prevent tooth loss.. Patients (63 nonsmokers, 23 smokers) with chronic generalized periodontitis who were undergoing SRP participated. Healing was evaluated based on PD, assessed at baseline and 8-16 wk after SRP. Intakes of fruits, vegetables, β-carotene, vitamin C, α-tocopherol, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were estimated using the Block 2005 food frequency questionnaire and a supplement questionnaire. Serum 25-hydroxyvitamin D concentrations were also measured. PD (% sites >3 mm) was modeled in multiple linear regression and analysis of covariance by tertile of intake and adjusted for age, sex, body mass index (BMI), baseline PD, examiner, gingival bleeding, and study duration.. In nonsmokers, PD was associated with fruit and vegetable, β-carotene, vitamin C, α-tocopherol, EPA, and DHA intakes (P < 0.05). PD was not significantly associated with ALA intake or serum 25-hydroxyvitamin D concentration. Significant associations that included supplements (β-carotene, vitamin C, α-tocopherol) were attenuated or lost, depending on the statistical model used. There were no significant associations within the group of smokers.. Dietary intakes of fruits and vegetables, β-carotene, vitamin C, α-tocopherol, EPA, and DHA are associated with reduced PD after SRP in nonsmokers, but not smokers, with chronic generalized periodontitis. These findings may lead to the development of dietary strategies to optimize healing after periodontal procedures. This trial was registered at clinicaltrials.gov as NCT02291835.

Topics: Adult; Aged; Aged, 80 and over; alpha-Linolenic Acid; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Body Mass Index; Chronic Disease; Cross-Sectional Studies; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Energy Intake; Female; Fruit; Humans; Inflammation; Linear Models; Male; Middle Aged; Nutrition Assessment; Periodontitis; Risk Factors; Smoking; Surveys and Questionnaires; Vegetables; Vitamin D

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3h. The onset of an adaptive response was observed at 5h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.

Topics: Administration, Inhalation; Animals; Antioxidants; Ascorbic Acid; Coal Ash; Female; Glutathione; Heart; Inflammation; Interleukin-6; Lung; Mice; Neutrophils; Oxidative Stress; Protein Carbonylation; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

Activated neutrophils secrete hypochlorous acid (HOCl) into the extracellular space of inflamed tissues. Because of short diffusion distance in biological fluids, HOCl-damaging effect is restricted to the extracellular compartment. The current study aimed at investigating the ability of nicotine, a component of tobacco and electronic cigarettes, to mediate HOCl-induced intracellular damage. We report, for the first time, that HOCl reacts with nicotine to produce nicotine chloramine (Nic-Cl). Nic-Cl caused dose-dependent damage to proliferating cell nuclear antigen (PCNA), a nuclear protein, in cultured mammalian lung and kidney cells. Vitamin C, vitamin E analogue (Trolox), glutathione, and N-acetyl-L-cysteine inhibited the Nic-Cl-induced PCNA damage, implicating oxidation in PCNA damage. These findings point out the ability of nicotine to mediate HOCl-induced intracellular damage and suggest antioxidants as protective measures. The results also raise the possibility that Nic-Cl can be created in the inflamed tissues of tobacco and electronic cigarette smokers and may contribute to smoking-related diseases.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Cell Line; Cell Proliferation; Chromans; Glutathione; Humans; Hypochlorous Acid; Inflammation; Kidney; Lung; Neutrophils; Nicotine; Oxidation-Reduction; Proliferating Cell Nuclear Antigen

Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems.. A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30-35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured.. The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor α [TNF-α], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase.. The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.

Topics: Animals; Ascorbic Acid; Blood Coagulation Disorders; Brain Injuries; Complement Activation; Disease Models, Animal; Endothelium; Female; Fibrinolysis; Hemorrhage; Inflammation; Shock, Hemorrhagic; Swine

Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis with inflammation. Investigations have suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. To provide further insights into beneficial effects of antioxidants in NASH prevention, we employed two manganese-superoxide dismutase/catalase mimetics, manganese N,N`-bis(salicyldene) ethylene diamine chloride (EUK-8) and manganese-3-methoxy N,N`-bis(salicyldene)ethylenediamine chloride (EUK-134), as two salen representatives and vitamin C as the standard antioxidant.. Experimental NASH was induced in Male N-Mary rats by feeding a methionine/choline-deficient (MCD) diet to rats for 10 weeks. The rats (n = 5, 30 mg/kg/day) were randomly assigned to receive vitamin C, EUK-8, EUK-134 or vehicle orally.. Administration of salens together with the MCD diet reduced the serum aminotransferases, glutathione transferase and alkaline phosphatase, cholesterol, and LDL contents. In addition, the EUK-8 and EUK-134 improved NASH pathological features in liver of MCD-fed rats.. EUK-8 and EUK-134 supplementation reduces NASH-induced abnormalities, pointing out that antioxidant strategy could be beneficial for prevention of NASH.

Topics: Animals; Antioxidants; Ascorbic Acid; Chelating Agents; Choline; Diet; Ethylenediamines; Fatty Liver; Inflammation; Liver; Male; Manganese Compounds; Methionine; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Rats

Using archival data, we conducted a secondary analysis to examine race differences in the relation of serum vitamins A, C, E and β-carotene to insulin resistance (IR), fasting insulin and glucose, high sensitivity C-reactive protein (hs-CRP), and leukocyte count in 176 non-smoking, healthy, white, and African American (AA) adults aged 18 to 65 years (48% women, 33% AA). We hypothesized that micronutrient concentrations would be associated with early risk markers of cardiometabolic diseases in a race-dependent manner. Fasting blood samples were analyzed for micronutrients, insulin, glucose, hs-CRP, and leukocyte count. Insulin resistance was estimated using the homeostatic model assessment. After adjusting for age, body mass index, gender, educational level, use of vitamin supplements, alcohol intake, leisure time physical activity, menopausal status, and total cholesterol, we observed that β-carotene was significantly associated with insulin resistance and fasting insulin in a race-dependent manner. Among AA, lower β-carotene levels were associated with higher estimates of insulin resistance and fasting insulin; whereas, these same associations were not significant for whites. Race also significantly moderated the relation of vitamin C to leukocyte count, with lower vitamin C being associated with higher leukocyte count only in AA but not whites. For all subjects, lower β-carotene was associated with higher hs-CRP. In AA, but not whites, lower levels of β-carotene and vitamin C were significantly associated with early risk markers implicated in cardiometabolic conditions and cancer. Whether or not lower levels of micronutrients contribute uniquely to racial health disparities is a worthwhile aim for future research.

Topics: Adiposity; Adolescent; Adult; Aged; Ascorbic Acid; beta Carotene; Biomarkers; Black or African American; Blood Glucose; C-Reactive Protein; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leukocyte Count; Male; Metabolic Diseases; Middle Aged; Racial Groups; Risk Factors; Vitamin A; Vitamin E; Vitamins; White People

We investigated the hypothesis that an antioxidant, Vitamin C, could attenuate abdominal aortic aneurysm (AAA) development in a rat model.. An AAA model induced by intraluminal infusion was created in 36 male Sprague Dawley rats, which were randomly distributed into three groups: Sham (saline infused, placebo treated), Control (elastase infused, placebo treated), and Vitamin C (elastase infused, vitamin C treated). Vitamin C and placebo were intraperitoneally injected, initiating 1 wk before the infusion and continuing throughout the study. The aortic dilatation ratio was measured, and aortic tissues were further examined using biochemical and histologic techniques.. Vitamin C attenuated the development of AAA, decreasing maximal aortic diameter by 25.8% (P < 0.05) and preserving elastin lamellae (P < 0.05). Vitamin C also decreased 8-hydroxyguanine (a marker of oxidative damage to DNA) and 8-isoprostane content (a marker of oxidative stress) in aortic tissues (P < 0.05, respectively). The proteins of matrix metalloproteinase (MMP)-2, MMP-9, and interleukin 6 were markedly downregulated (P < 0.05, respectively), accompanied with notably reduced messenger RNA expression of tumor necrosis factor-α, MMP-2/9, and interleukin 1β (P < 0.05, respectively). However, messenger RNA of tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 were both significantly upregulated in Vitamin C group. Vitamin C treatment had no significant effect on systolic blood pressure (P > 0.05).. Vitamin C attenuated AAA development in an elastase-induced rat model via crucial protective effect, which was mediated by an increased level of antioxidant in cooperation with preserving elastin lamellae, inhibiting matrix-degrading proteinases and suppressing inflammatory responses.

Topics: Animals; Antioxidants; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Ascorbic Acid; Blood Pressure; Disease Models, Animal; Drug Evaluation, Preclinical; Inflammation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Oxidative Stress; Pancreatic Elastase; Random Allocation; Rats

Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects.

Topics: Animals; Apoptosis; Ascorbic Acid; Brain; Cognition; Inflammation; Male; Maze Learning; Mice; Motor Activity; Nanomedicine; Nanotubes, Carbon; Neuroprotective Agents; Oxidative Stress

This study investigated the effects of ascorbic acid and N-acetyl cysteine (NAC) antioxidants on the development of myringosclerosis (MS) in an experimental model.. Myringotomies were performed in the ears of 15 guinea pigs, and Spongostan pieces were placed on the perforated regions of the tympanic membrane. The subjects were divided randomly into three groups and treated with three different solutions on the Spongostan-group 1: (control, 0.9% saline), group 2 (ascorbic acid), and group 3 (NAC). On day 15 after treatment, specimens from the tympanic membranes were obtained and examined via light microscopy. Sclerosis and inflammation scores and the tympanic membrane thicknesses were evaluated. Immunohistochemical methods were used to evaluate the expression of VEGF, TGF-β, iNOS, and IL1-β in all groups.. Lower sclerosis and inflammation scores and reduced tympanic membrane thicknesses were observed in groups treated with NAC or ascorbic acid compared with the control group. Immunohistochemical studies revealed significantly less expression of VEGF, TGF-β, and iNOS in groups 2 and 3 compared with group 1. Additionally, IL1-β expression was significantly less in group 3 than in group 1. Compared with group 1, group 2 animals exhibited reduced inflammation in the lamina propria, fewer active fibroblasts, less leukocyte infiltration, and decreased thickness of the vessels; group 3 animals exhibited decreased numbers of active fibroblasts and collagen fibers in the lamina propria.. Inflammation scores, cellular infiltration, and expression of VEGF, TGF-β, and iNOS were reduced by ascorbic acid and/or NAC treatments, thereby decreasing MS development. Decreased expression of IL1-β was observed only in animals treated with NAC.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Female; Fibrin Foam; Fibroblasts; Free Radical Scavengers; Guinea Pigs; Hemostatics; Immunohistochemistry; Inflammation; Leukocytes; Microscopy; Mucous Membrane; Myringosclerosis; Nitric Oxide Synthase; Random Allocation; Transforming Growth Factor beta; Tympanic Membrane; Vascular Endothelial Growth Factor A

Respiratory allergic disease is an inflammatory condition accompanied by oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants may have a therapeutic effect. In this study, the effects of choline chloride in combination with antioxidants were evaluated via the intranasal route in a mouse model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and 14 and challenged on days 25-30 with cockroach extract (CE) and with a booster challenge on day 38. They were treated with choline chloride (ChCl; 1mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/kg) alone or in combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs, and spleen. Mice immunized with CE showed a significant increase in airway hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative stress markers intracellular reactive oxygen species and 8-isoprostanes compared to the phosphate-buffered saline control group. A significant decrease was observed in these parameters with all the treatments (p<0.01). The highest decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to the normal level. This group also showed the highest decrease in airway inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF-κB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase activity, which was decreased significantly in CE-immunized mice, was restored to normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized mice and was restored to normal by combination treatment. The combination treatment induced FOXP3(+) cells in splenocyte culture, responsible for the upregulation of IL-10. In conclusion, the combination of choline chloride, vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and oxidative stress, probably by causing IL-10 production by FOXP3(+) cells, and possesses therapeutic potential against allergic airway disease.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Asthma; Bronchoalveolar Lavage Fluid; Choline; Cockroaches; Dinoprost; Drug Combinations; Eosinophil Peroxidase; Glutathione Peroxidase; Immunoglobulin E; Immunoglobulin G; Inflammation; Interleukin-10; Interleukin-4; Interleukin-5; Lipotropic Agents; Lung; Mice; Mice, Inbred BALB C; Oxidative Stress; Reactive Oxygen Species; Respiratory Hypersensitivity; Selenium; Spleen; Th2 Cells; Transcription Factor RelA

To investigate the effects of pharmacologic ascorbate (vitamin C) against Influenza A/CA/7/09 (H1N12009).. BALB/c mice inoculated intranasally with influenza virus were treated with ascorbate (3 mg/g) twice daily by intraperitoneal (i.p.) injection for up to 14 d. Control groups received an equivalent volume of normal saline. Body weights were measured daily. To quantify the level of viral replication in the respiratory tract, the mice were euthanized and lungs removed and prepared as whole lung homogenates.Viral titers were determined by TCID50 assay in MDCK cells. Cytokine titers were determined by ELISA following the manufacturer's protocol (IL-1β, IL-6, TNF-α, IFN-α). For lung histopathologic evaluation, lungs were fixed with 10% neutral-buffered formalin at time of isolation, and then coded, processed into paraffin blocks, sectioned onto glass slides and stained (hematoxylin and eosin).Slides were examined and scored by a pathologist.. Mice infected with influenza virus and treated with pharmacologic ascorbate had higher survival and less weight loss, and had lung viral titers reduced by as much as 10 to 100-fold compared to the controls. Pathologic study of the lungs showed that the treated animals had little inflammation (bronchiolitis, perivasculitis, alveolitis, and vasculitis) compared to the controls.IL-1, IL-6, and IFN-alpha lung levels were lower in the treated animals compared to the controls.. Pharmacologic ascorbate is a pro-oxidant that eliminates influenza virus in the lung, and therefore reduces lung inflammation and lowers death rate in this mouse model.

Topics: Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Inflammation; Influenza A virus; Interleukin-6; Lung; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Tumor Necrosis Factor-alpha; Viral Load

Canonical neutrophil antimicrobial effector mechanisms, such as degranulation, production of reactive oxygen species, and release of neutrophil extracellular traps (NETs), can result in severe pathology. Activation of neutrophils through immune complexes (ICs) plays a central role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report that immobilized ICs (iICs), which are hallmarks of several autoimmune diseases, induce the release of NETs from primary human neutrophils. The iIC-induced NET formation was found to require production of reactive oxygen species by NADPH oxidase and myeloperoxidase and to be mediated by FcγRIIIb. Blocking of the β2 integrin macrophage-1 Ag but not lymphocyte function-associated Ag-1 abolished iIC-induced NET formation. This suggests that FcγRIIIb signals in association with macrophage-1 Ag. As intracellular signaling pathways involved in iIC-induced NET formation we identified the tyrosine kinase Src/Syk pathway, which downstream regulates the PI3K/Akt, p38 MAPK, and ERK1/2 pathways. To our knowledge, the present study shows for the first time that iICs induce NET formation. Thus, we conclude that NETs contribute to pathology in autoimmune inflammatory disorders associated with surface-bound ICs.

Topics: Aminopyrine; Antigen-Antibody Complex; Antioxidants; Ascorbic Acid; Autoimmune Diseases; Butadienes; CD11a Antigen; CD18 Antigens; Cell Degranulation; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases; GPI-Linked Proteins; Humans; Imidazoles; Inflammation; Intracellular Signaling Peptides and Proteins; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Mesalamine; Neutrophil Activation; Neutrophils; Nitriles; Onium Compounds; p38 Mitogen-Activated Protein Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-akt; Pyridines; Pyrimidines; Reactive Oxygen Species; Receptors, IgG; src-Family Kinases; Syk Kinase

Topics: Antioxidants; Ascorbic Acid; Humans; Inflammation; Osteoarthritis, Knee

Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited.. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages.. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses.. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.

Topics: Animals; Ascorbic Acid; Blotting, Western; Cell Line; Humans; Inflammation; Lipopolysaccharides; Macrophages; Macrophages, Peritoneal; Mice; Mice, Knockout; Mice, Transgenic; Microscopy, Fluorescence; Peritonitis; Real-Time Polymerase Chain Reaction; Thioglycolates

Visceral obesity is more common in the Arab population and more closely related to morbidity, including diabetes and related cardiovascular diseases (CVD). Possible mechanisms that link visceral fat/obesity to diabetes and CVD complications include inflammation and increased oxidative stress; however, few data are available from the Arab population. Our aim was to determine whether increased adiposity in obese diabetic United Arab Emirates citizens is associated with sub-clinical inflammation and/or increased oxidative stress. A hundred diabetic patients who were part of a randomized controlled trial of nutritional supplements had their baseline characteristics assessed from anthropometric and clinical data following informed written consent. We used WHO figures to classify general and central obesity. Fasting blood samples were collected for the measurement of antioxidants and markers of oxidative damage and inflammation. We found that increased adiposity measured by both body mass index and waist circumference was associated with increased C-reactive protein (CRP) and decreased vitamin C after adjusting for age, duration and treatment of diabetes (p < 0.05). Although there is a clear trend of increased inflammatory markers, notably CRP, and decreased antioxidants with increased BMI and waist circumference in both men and women, the results are statistically significant for women only. CRP were also inversely associated with HDL. Overall, we found that BMI underestimates the rates of obesity compared to waist circumference and that increased adiposity is associated with increased inflammation and decreased HDL and antioxidant status.

Topics: Adiposity; Ascorbic Acid; Biomarkers; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Obesity; Oxidative Stress; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; United Arab Emirates; Vitamin A; Vitamin E; Waist Circumference

Low-grade inflammation is an independent risk factor for cardiovascular disease. Relationships between the antioxidant status and inflammatory biomarkers could give new insights into cardiovascular disease prevention. We investigated long-term associations between the antioxidant nutrient (vitamin C, α-tocopherol, β-carotene) status and C-reactive protein (CRP) in a population-based cohort.. Subjects included in the French SU.VI.MAX trial study who had available data on baseline (1994-1995) blood nutrient concentrations and CRP measurements 12 years later (2007-2009) were included. Associations between baseline antioxidant circulating concentrations and elevated CRP (>3 mg/l) were investigated in multivariate logistic regression models. Subgroup analyses were performed according to gender, supplementation group of the initial trial, smoking status, and alcohol intake.. Serum α-tocopherol (n = 2,060) and vitamin C (n = 1,719) concentrations [odds ratio (OR) and 95% confidence interval (95% CI) quintile 5 vs. 1: OR 1.10 (95% CI 0.71-1.73), p for trend = 0.533, vs. OR 0.79 (95% CI 0.48-1.29), p for trend = 0.121, respectively] were not associated with elevated CRP concentrations. The β-carotene status (n = 2,048) was inversely associated with elevated CRP [adjusted OR quintile 5 vs. 1: OR 0.61 (95% CI 0.38-0.98), p for trend = 0.01]. Subgroup analyses showed that associations were stronger in women (p for trend = 0.004), never smokers (p for trend = 0.009) and subjects in the supplementation group (p for trend = 0.002).. Our results suggest that the β-carotene status may be inversely associated with low-grade inflammation in the long term.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; C-Reactive Protein; Cohort Studies; Female; France; Humans; Inflammation; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect.. Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed.. The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp.. VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.

Topics: Animals; Ascorbic Acid; Enzyme Inhibitors; Heme Oxygenase-1; Inflammation; Interleukin-6; Kidney; Liver; Lung; Multiple Organ Failure; Protoporphyrins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha; Vitamins

In pathological conditions, oxidative burst generates hyaluronan (HA) fragmentation with a consequent increase in the number of small HA oligosaccharides. These fragments are able to stimulate an inflammatory response in different cell types by activating the CD44 and the toll-like receptors 4 (TLR-4) and 2 (TLR-2). The stimulation of CD44 and TLRs in turn activates the NF-kB which induces the production of several pro-inflammatory mediators that amplify and perpetuate inflammation. We aimed to study the antioxidant effect of the SOD mimic, synthetic manganese porphyrin, Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP(5+)) on preventing HA degradation in mouse articular chondrocytes stimulated with Fe (II) plus ascorbate. Fe (II) plus ascorbate stimulation induced oxidative burst confirmed by high levels of hydroxyl radical/peroxynitrite production, increased lipid peroxidation and HA degradation. HA fragments highly induced mRNA expression and the related protein production of CD44, TLR-4 and TLR-2, NF-kB activation and significantly up-regulated the inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and other pro-inflammatory mediators, i.e. matrix metalloprotease 13 (MMP-13) and inducible nitric oxide synthase (iNOS). Treatment of cells with MnTM-2-PyP(5+)was able to attenuate oxidative burst, HA degradation and NF-kB activation, and markedly decreased mRNA expression of CD44, and TLRs and the related protein synthesis, as well as the levels of up-regulated inflammatory mediators. Adding a specific HA-blocking peptide (PEP-1) to cells significantly reduced all the inflammatory parameters up-regulated by Fe (II) plus ascorbate, and increased MnTM-2-PyP(5+) activity. These findings suggest that HA degradation plays a key role in the initial inflammatory response of cartilage and antioxidants and could be a useful tool to prevent the propagation of this mechanism.

Topics: Animals; Ascorbic Acid; Cartilage, Articular; Chondrocytes; Cysteamine; Gene Expression Regulation; Hyaluronan Receptors; Hyaluronic Acid; Inflammation; Interleukin-1beta; Iron; Lipid Peroxidation; Male; Matrix Metalloproteinase 13; Metalloporphyrins; Mice; Molecular Weight; NF-kappa B; Nitric Oxide Synthase Type II; Oxidation-Reduction; Peptides; Reactive Oxygen Species; RNA, Messenger; Superoxide Dismutase; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU.. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay.. Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation.. All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

Topics: Acetylcysteine; Alkaptonuria; Antioxidants; Ascorbic Acid; Cell Line; Chondrocytes; Cytokines; Humans; Inflammation; Lipid Peroxidation; Phytic Acid; Serum Amyloid A Protein; Taurine; Thioctic Acid

The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Intraluminal pro-oxidants from ingested nutrients especially iron salts and ascorbic acid frequently consumed together, can lead to catalytic formation of oxygen-derived free radicals that ultimately overwhelm the cellular antioxidant defense and lead to cell damage.. Since the mechanisms remain sketchy, efforts have been exerted to evaluate the role of epigenetics in modulating components of endogenous enzymatic antioxidants in the intestine. To this end, Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-generating system.. Fe/Asc induced a significant increase in lipid peroxidation as reflected by the elevated formation of malondialdehyde along with the alteration of antioxidant defense as evidenced by raised superoxide dismutase 2 (SOD2) and diminished glutathione peroxidase (GPx) activities and genes. Consequently, there was an up-regulation of inflammatory processes illustrated by the activation of NF-κB transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IκB. Assessment of promoter's methylation revealed decreased levels for SOD2 and increased degree for GPx2. On the other hand, pre-incubation of Caco-2/15 cells with 5-Aza-2'-deoxycytidine, a demethylating agent, or Trolox antioxidant normalized the activities of SOD2 and GPx, reduced lipid peroxidation and prevented inflammation.. Redox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.

Topics: Antioxidants; Ascorbic Acid; Caco-2 Cells; Cell Line, Tumor; Cell Survival; Cyclooxygenase 2; DNA Methylation; Epigenesis, Genetic; Epithelial Cells; Free Radicals; Gene Expression; Glutathione Peroxidase; Humans; I-kappa B Kinase; Inflammation; Interleukin-6; Intestines; Iron; Lipid Peroxidation; Malondialdehyde; NF-kappa B; Promoter Regions, Genetic; Superoxide Dismutase; Up-Regulation

The objective was to examine the inhibitory effects of citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells, focusing on the antiproliferative mechanism of action of the flavonoid apigenin related to the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway.. Flavonoids, limonoids, phenolic acids, and ascorbic acid were tested for cytotoxic effects on BxPC-3 and PANC-1 cells; apigenin was the most potent (IC50 = 23 and 12 μM for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 μM for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G2 /M phase (36 and 32% at 50 μM for BxPC-3 and PANC-1, respectively) with concomitant decrease in the expression of cyclin B1. Apigenin activated the mitochondrial pathway of apoptosis (44 and 14% at 50 μM for BxPC-3 and PANC-1, respectively) and modified the expression of apoptotic proteins. Apigenin highly upregulated the expression of cytokine genes IL17F (114.2-fold), LTA (33.1-fold), IL17C (23.2-fold), IL17A (11.3-fold), and IFNB1 (8.9-fold) in BxPC-3 cells, which potentially contributed to the anticancer properties.. Flavonoids have a protective role in pancreatic cancer tumorigenesis.

Topics: Antineoplastic Agents, Phytogenic; Apigenin; Apoptosis; Ascorbic Acid; Catalytic Domain; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Citrus; Cytokines; Drug Screening Assays, Antitumor; Flavonoids; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Inflammation; NF-kappa B; Pancreatic Neoplasms; Signal Transduction

Ascorbic acid (vitamin C, ascorbate) is a key water soluble antioxidant that, when administered in doses well above its recommended dietary allowance, may have preventative and therapeutic value against a number of pathologies. The intravenous administration of high dose ascorbate (IVC) has increased in popularity among complementary and alternative medicine practitioners: thousands of patients received IVC, at an average dose of 0.5 g/kg, without significant side effects. While IVC may have a variety of possible applications, it has generated the most interest for its potential use in treating cancer.. Medical records of patients with cancer treated with IVC at the Riordan Clinic were retrospectively reviewed. Cancer patients, for whom plasma ascorbate concentration data before and after treatment were available, along with C-reactive protein (CRP) measurements, were chosen for analysis.. The results of the analysis can be summarized as follows. IVC produces peak plasma ascorbate concentrations on the order of ten millimolars with lower peak plasma concentrations obtained in cancer patients as compared to healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion. High inflammation or tumor burdens, as measured by CRP or tumor antigen levels, tend to lower peak plasma ascorbate levels after IVC. When compared to patients with localized tumors, patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate concentrations.. The data indicate that, while potentially therapeutic plasma ascorbate concentrations can be achieved with IVC, levels attained will vary based on tumor burden and degree of inflammation (among other factors). Evidence suggests that IVC may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers, Tumor; C-Reactive Protein; Female; Humans; Inflammation; Male; Middle Aged; Neoplasms

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5 mg/kg), LPS + melatonin (1 mg/kg), or LPS + melatonin (10 mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5 h after the onset of endotoxemia. There were significant higher levels of SOD (p < 0.05), IL-6 (p < 0.01), and IL-10 (p < 0.05) during nighttime endotoxemia compared with daytime. At daytime, melatonin 1 and 10 mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p < 0.05). At nighttime, melatonin reduced the levels of MDA and increased DHA (p < 0.05). Additionally, 10 mg melatonin resulted in lower levels of AA during daytime (p < 0.05). No dose relationship of melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model.

Topics: Acute-Phase Reaction; Animals; Antioxidants; Ascorbic Acid; Circadian Rhythm; Darkness; Disease Models, Animal; Endotoxemia; Inflammation; Interleukin-10; Interleukin-6; Light; Lipopolysaccharides; Male; Malondialdehyde; Melatonin; Oxidative Stress; Oxygen; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Dietary patterns and biomarkers of inflammation have been scarcely associated. The aim was to assess dietary factors associated with subclinical inflammation among girls.. Fasting blood samples were collected from 12- to 17-year old girls (n=219) to measure adiponectin, leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels. Body mass index (BMI) and waist-to-height ratio (WHtR), and food intake were also measured. Western (WDP) and Mediterranean (MDP) dietary patterns were identified.. BMI and WHtR were associated with adiponectin, leptin and hs-CRP (the last, only associated with BMI). Intakes of β-carotene equivalents and vitamin C were associated with adiponectin; saturated fatty acids (SFA), vitamin A, manganese and selenium with leptin; linoleic acid with PAI-1; and oleic acid and vitamin E with IL-6. Selenium was inversely associated with adiponectin, whereas magnesium was positively associated with IL-6. MDP was associated with higher plasma concentrations of adiponectin (β=0.174, P<0.05); after adjustment for BMI, associations were not significant (β=0.144, P=0.076). WDP was negatively associated with adiponectin (β=-0.177, P<0.05) and positively with IL-6 (β=0.183, P<0.05).. Subclinical inflammation is detectable with increasing BMI and also WHtR. Measures of adiposity (BMI and WHtR) are significant predictors of adiponectin, leptin and hs-CRP. Dietary patterns per se have a small role in affecting inflammatory markers among adolescents.

Topics: Adiponectin; Adolescent; Ascorbic Acid; beta Carotene; Biomarkers; Body Height; Body Mass Index; C-Reactive Protein; Child; Diet; Fatty Acids; Female; Humans; Inflammation; Interleukin-6; Leptin; Linoleic Acid; Manganese; Oleic Acid; Plasminogen Activator Inhibitor 1; Selenium; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin E; Waist Circumference

The objective of this cross-sectional study was to evaluate the relationship between micronutrient status and obesity, lipids, insulin resistance and chronic inflammation in children. Weight, height, waist circumference and body composition (dual-energy X-ray absorptiometry (DEXA)) were determined in 197 school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP), zinc, iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin E:lipids were negatively associated with Body Mass Index (BMI), waist-to-height ratio (WHR) and body and abdominal fat (p < 0.05). Vitamin A was positively associated with BMI, BMI-for-age, WHR and abdominal fat (p < 0.05). Iron and vitamin E:lipids were negatively associated with insulin (p < 0.05). Vitamins A, C and E and iron were negatively associated with CRP (p < 0.05). Interaction analysis showed that children who were overweight and obese who also had low concentrations of vitamin A had higher CRP and lower triglycerides (p < 0.1), children with low vitamin E had significantly lower glucose and triglycerides (p < 0.1) and higher low-density lipoprotein (LDL) concentrations (p < 0.05), and children with low zinc concentrations had higher insulin resistance compared with children with adequate weight (p < 0.05). In conclusion, low vitamin C concentration and vitamin E:lipids were associated with obesity. Furthermore, low concentrations of zinc, vitamins A and E in children who were overweight and obese were associated with lipids, inflammation and insulin resistance.

Topics: Ascorbic Acid; Blood Glucose; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Child; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin; Insulin Resistance; Iron, Dietary; Male; Mexico; Micronutrients; Motor Activity; Nutrition Assessment; Pediatric Obesity; Socioeconomic Factors; Triglycerides; Vitamin D; Waist Circumference; Zinc

The main objective of the study was to analyze the potential ability of vitamins E, C, and D, used as nutritional supplements, in averting inflammation and oxidative stress in the course of diabetes mellitus.. Male mice were divided into eight groups. Diabetes was induced (groups II, VI, VII, and VIII) by an intraperitoneal injection of streptozotocin (STZ). The third and sixth groups were given vitamin C (50 mg/kg) 3 times per week, the fourth and seventh groups were given vitamin E (300 mg/kg) 3 times per week, and the fifth and eight groups were given vitamin D (2000 IU/day). Interleukin-6 levels were measured in serum. Glutathione (GSH) levels and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were measured in the liver tissue.. STZ resulted in a significant decrease in all tested enzymes and glutathione levels, and an increase in IL-6 level in comparison to control animals (p < 0.05). Mice treated with vitamins had a significantly (p < 0.05) higher content of enzymes and glutathione in liver than diabetic mice, however IL-6 concentration showed a significant decrease. Concurrent administration of STZ and vitamins caused a significant increase (compared to the diabetes group) in SOD, CAT, GPx, GSH content, and a decrease in IL-6 levels (p < 0.05).. These results indicate the preventive role of vitamin C, E, and D against STZ-induced diabetic oxidative stress and inflammation. Hence these vitamins could be used as an adjuvant therapy for the prevention and/or management of diabetes.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Catalase; Diabetes Mellitus, Experimental; Dietary Supplements; Glutathione; Glutathione Peroxidase; Inflammation; Interleukin-6; Liver; Male; Mice; Oxidative Stress; Superoxide Dismutase; Vitamin D; Vitamin E

Myeloperoxidase is a neutrophil enzyme that promotes oxidative stress in numerous inflammatory pathologies. It uses hydrogen peroxide to catalyze the production of strong oxidants including chlorine bleach and free radicals. A physiological defense against the inappropriate action of this enzyme has yet to be identified. We found that myeloperoxidase oxidized 75% of the ascorbate in plasma from ceruloplasmin knock-out mice, but there was no significant loss in plasma from wild type animals. When myeloperoxidase was added to human plasma it became bound to other proteins and was reversibly inhibited. Ceruloplasmin was the predominant protein associated with myeloperoxidase. When the purified proteins were mixed, they became strongly but reversibly associated. Ceruloplasmin was a potent inhibitor of purified myeloperoxidase, inhibiting production of hypochlorous acid by 50% at 25 nm. Ceruloplasmin rapidly reduced Compound I, the Fe(V) redox intermediate of myeloperoxidase, to Compound II, which has Fe(IV) in its heme prosthetic groups. It also prevented the fast reduction of Compound II by tyrosine. In the presence of chloride and hydrogen peroxide, ceruloplasmin converted myeloperoxidase to Compound II and slowed its conversion back to the ferric enzyme. Collectively, our results indicate that ceruloplasmin inhibits myeloperoxidase by reducing Compound I and then trapping the enzyme as inactive Compound II. We propose that ceruloplasmin should provide a protective shield against inadvertent oxidant production by myeloperoxidase during inflammation.

Topics: Animals; Ascorbic Acid; Ceruloplasmin; Enzyme Inhibitors; Humans; Hypochlorous Acid; Inflammation; Mice; Mice, Knockout; Oxidation-Reduction; Peroxidase; Protein Binding

Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body's natural defenses against inflammatory diseases.. To define the polyphenols extracted from dried apple peels (DAPP) and determine their antioxidant and anti-inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidative stress (OxS) and inflammation induced by iron-ascorbate (Fe/Asc) and lipopolysaccharide (LPS), respectively.. The combination of HPLC with fluorescence detection, HPLC-ESI-MS TOF and UPLC-ESI-MS/MS QQQ allowed us to characterize the phenolic compounds present in the DAPP (phenolic acids, flavonol glycosides, flavan-3-ols, procyanidins). The addition of Fe/Asc to Caco-2/15 cells induced OxS as demonstrated by the rise in malondialdehyde, depletion of n-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubation with DAPP prevented Fe/Asc-mediated lipid peroxidation and counteracted LPS-mediated inflammation as evidenced by the down-regulation of cytokines (TNF-α and IL-6), and prostaglandin E2. The mechanisms of action triggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-κB, respectively. These actions were accompanied by the induction of Nrf2 (orchestrating cellular antioxidant defenses and maintaining redox homeostasis), and PGC-1α (the "master controller" of mitochondrial biogenesis).. Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.

Topics: Antioxidants; Ascorbic Acid; Caco-2 Cells; Cyclooxygenase 2; Ferrous Compounds; Gastric Mucosa; Gene Expression; Glutathione Reductase; Humans; Inflammation; Interleukin-6; Lipid Peroxidation; Lipopolysaccharides; Malus; Models, Biological; NF-kappa B; Oxidative Stress; Polyphenols; Superoxide Dismutase; Tumor Necrosis Factor-alpha

To investigate the efficacy of combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) in reducing ethanol-induced hepatotoxicity.. Rats were maintained for 90 days and grouped as follows: I-control rats, II-ethanol, III-alpha-tocopherol, IV-ethanol+alpha-tocopherol, V-AA, VI-ethanol+ascorbic acid, VII-alpha-tocopherol+ascorbic acid, VIII-ethanol+alpha-tocopherol+ascorbic acid. At the end of the experimental period, markers of hepatic function, oxidative stress, and the expression of markers of inflammation and fibrosis were assayed.. The markers of hepatic function, lipid peroxidation products, protein carbonyls, and the expression of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, cytochrome P4502E1, and collagen Type I were elevated after ethanol administration. All these parameters were reduced in the ethanol group administered AT and AA in combination. The activities of antioxidant enzymes which were reduced by ethanol administration were enhanced on combined administration of AT and AA. The reduction in hepatic fibrosis was almost 20% more in AT and AA co-administered group compared with AT and AA alone treated groups.. Combined administration of fat soluble AT and water soluble AA was beneficial against ethanol-induced hepatotoxicity. This may be due to their different subcellular localizations.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Biomarkers; Chromatography, High Pressure Liquid; Collagen Type I; Drug Therapy, Combination; Ethanol; Inflammation; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha

Considerable evidence supports the presence of oxidative stress in cystic fibrosis (CF). The disease has long been associated with both increased production of reactive oxygen species and impaired antioxidant status, in particular during the chronic pulmonary infection with Pseudomonas aeruginosa, which is the main cause of morbidity and mortality in CF. Guinea pigs are unable to synthesize ascorbate (ASC) or vitamin C, a major antioxidant of the lung, and thus like human beings rely on its presence in the diet. On this basis, guinea pigs receiving ASC-deficient diet have been used as a model of oxidative stress. The aim of our study was to investigate the consequences of a 7-day biofilm-grown P. aeruginosa lung infection in 3-month-old guinea pigs receiving either ASC-sufficient or ASC-deficient diet for at least 2 months. The animals receiving ASC-deficient diet showed significantly higher mortality during infection and increased respiratory burst of peripheral polymorphonuclear neutrophils (PMNs) compared with the animals receiving ASC sufficient diet. The inflammatory response at the site of lung infection consisted of PMNs and mononuclear leucocytes (MN), and higher PMN/MN ratios were present in animals on ASC-deficient diet compared with animals on ASC sufficient diet. Measurements of the ASC levels in the lung were significantly decreased in infected compared with non-infected animals. Interestingly, the infection by itself decreased the antioxidant capacity of the plasma (measured as plasma oxidizability) more than the ASC-deficient diet, suggesting a high consumption of the antioxidants during infection. Our data show that poor antioxidant status exacerbates the outcome of biofilm-related infections.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biofilms; Disease Models, Animal; Female; Guinea Pigs; Inflammation; Leukocytes, Mononuclear; Lung Diseases; Neutrophils; Oxidative Stress; Pseudomonas aeruginosa; Pseudomonas Infections

Oxidative stress contributes to myonecrosis in the dystrophin-deficient fibers of mdx mice and in Duchenne's muscular dystrophy. We examined the effects of ascorbic acid (AA), an antioxidant and free radical scavenger, on the dystrophic diaphragm muscle.. Mdx mice (14 d old) received AA for 14 d. Control mdx mice received saline. The muscle damage was visualized by the penetration of Evans blue dye into myofibers and the extent of inflammation was assessed by histologic analysis. Creatine kinase levels were measured for the biochemical evaluation of muscle fiber degeneration. The levels of tumor necrosis factor-α (a proinflammatory cytokine) and 4-hydroxynonenal (a marker of lipid peroxidation) were analyzed by immunoblotting.. Ascorbic acid decreased creatine kinase levels, myonecrosis, inflammation, and the levels of tumor necrosis factor-α and 4-hydroxynonenal.. The present results suggest that AA plays a protective role in dystrophic muscle degeneration, possibly by decreasing reactive oxygen species, and support further investigations of AA as a potential therapy for dystrophinopathies.

Topics: Aldehydes; Animals; Antioxidants; Ascorbic Acid; Creatine Kinase; Diaphragm; Dystrophin; Female; Inflammation; Male; Mice; Mice, Inbred mdx; Muscle Fibers, Skeletal; Muscular Dystrophies; Necrosis; Oxidative Stress; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

The aim of the study was to determine the effects of single intraperitoneal injections of zymosan A on changes in the content of ascorbic acid (ASC) in the brain, liver, spleen and kidneys of mature male mice, line Swiss. The experiments were carried out on 54 mice divided into 3 control groups and 6 experimental groups. Samples for analysis were collected after 3 h (experimental group I), 6 h (experimental group II) and 24 h (experimental group III) after the injection of zymosan A at the dose of 1 mg/kg body weight (b.w.). For groups IV, V and VI, the organs were removed at the same time as for the previous groups, but the animals were administered zymosan A at the dose of 100 mg/kg b.w. The content of ASC was then determined. The results showed that zymosan A significantly reduced the content of ASC in the brain of the mice in all the experimental groups, in the spleen in all the experimental groups except of group I (after 3 h since injection of zymosan A at 1 mg/kg b.w.), in the liver only in experimental groups IV, V and VI (after the injection of zymosan A at 100 mg/kg b.w.), while in the kidneys the effects were observed for groups III, V and VI. The data suggest that the observed decrease in the content of ASC is caused by the oxidative activity of zymosan A.

Topics: Animals; Ascorbic Acid; Inflammation; Male; Mice; Zymosan

This study examined the effect of weight loss after 3, 6 and 12 months of Roux-en-Y Gastric Bypass (RYGB) on energy intake and on several biomarkers of oxidative stress such as levels of vitamin C, beta-carotene, vitamin E (diet/blood), nitric oxide metabolites (NOx), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and activity of catalase (CAT).. Study with a control group (CG), assessed once, and a bariatric group (BG) assessed at the basal period as well as at 3, 6 and 12 months post-surgery; both groups were composed of 5 men and 31 women (n=36). Age was 38.7 ± 9.4 and 39.6 ± 9.2 years old and body mass index (BMI) was 22.2 0 ± 2.1 and 47.6 ± 9.1 kg/m(2), respectively. The variance measure quoted was SEM.. The body weight at 12 months was 35.8 ± 1.0% (P<0.001) lower than that of the basal period. At the basal period BG showed higher levels of NOx (P=0.007) and TBARS (P<0.001) and lower levels of vitamins C and E (P<0.001) compared with CG. After 3 months the activity of MPO was decreased (P<0.001). Six months after surgery GSH levels were decreased (P=0.037), whereas CAT activity was increased (P=0.029). After 12 months levels of NOx (P=0.004), TBARS (P<0.001), beta-carotene (P<0.001) and vitamin E (P<0.001) were decreased, whereas those of vitamin C (P<0.001) were increased compared with controls.. RYGB followed by a daily vitamin supplement apparently attenuated pro-inflammatory and oxidative stress markers 1 year after surgery, but additional antioxidant supplementation appears necessary.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Body Mass Index; Case-Control Studies; Catalase; Diet; Dietary Supplements; Energy Intake; Female; Follow-Up Studies; Gastric Bypass; Glutathione; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Peroxidase; Prospective Studies; Thiobarbituric Acid Reactive Substances; Vitamin E; Weight Loss

Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

Topics: Abdomen; Acute Lung Injury; Animals; Ascorbic Acid; Biomarkers; Blood Coagulation; Bronchoalveolar Lavage; Cell Line; Cytoskeletal Proteins; Humans; Inflammation; Ion Channels; Ion Transport; Lung; Male; Mice; Mice, Inbred C57BL; Neutrophils; Peritonitis; Permeability; Pulmonary Alveoli; Respiratory Mucosa; Sepsis; Sodium-Potassium-Exchanging ATPase

An important component of postoperative management includes alleviation of hepatic ischemia-reperfusion (I/R) injury, which commonly results from liver surgery. EPC-K1 is a hydroxyl radical scavenger reported to have mitigating effects on I/R injury in many organs. This study evaluates the effects of EPC-K1 on hepatic I/R injury.. Rats were injected subcutaneously with either EPC-K1 (100 mg/kg) or saline. The hepatic artery and left branch of the portal vein were clamped for 45 min under general anesthesia. Indicators of liver function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and of liver tissue damage were evaluated after 6h and 24h of reperfusion. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein were measured, and apoptosis was quantified via caspase 3/7 activity and TUNEL assay.. AST, ALT, and LDH levels increased significantly as a result of hepatic I/R injury, but were attenuated by EPC-K1 administration. Histologic findings revealed that normal structure of the hepatic parenchyma was maintained in rats pretreated with EPC-K1. TNF-α, IL-6, and HMGB1 levels rose significantly after reperfusion, together with activation of the inflammatory response. However, EPC-K1 administration suppressed levels of inflammatory markers and attenuated the inflammatory response. Moreover, EPC-K1 administration prevented apoptosis as determined by inhibition of caspase 3/7 activity and a decrease in apoptotic cells.. Results demonstrate that EPC-K1 inhibits the inflammatory response and suppresses apoptosis during hepatic I/R injury. This suggests that EPC-K1 has hepatoprotective effects, and may be a valuable and novel therapeutic agent in the clinical setting.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Aspartate Aminotransferases; HMGB1 Protein; Inflammation; Injections, Subcutaneous; Interleukin-6; L-Lactate Dehydrogenase; Liver; Male; Models, Animal; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha; Vitamin E

To investigate whether α-tocopherol and ascorbic acid have effect on the suppression of inflammation in the early postoperative period after open heart surgery.. A total of 59 patients who had undergone cardiopulmonary bypass (CPB) in the Cardiovascular Surgery Department of a tertiary center between June 2008 and December 2008 were retrospectively investigated. The study group consisted of 34 patients (25 men, 9 women) to whom ascorbic acid (500  mg/day) and α-tocopherol (300  mg/day) were administered on the day of operation (0th day) and the first four consecutive postoperative days. In contrast, 25 controls (20 men, 5 women) received no additional anti-inflammatory medications. The two groups were compared in terms of demographics, blood parameters such as C-reactive protein (CRP) and white blood cell (WBC) count, and durations of cross-clamp and CPB.. In the control group, CRP levels were found to be increased on the first postoperative day (P < 0.001) and CRP levels were correlated with triglyceride levels on the day of operation (P = 0.009) and the first postoperative day (P = 0.021). On the second postoperative day WBC count was found to be decreased (P = 0.008) and correlated with glucose level (P < 0.005). In the study group, CRP levels were found to be inversely correlated with serum high-density lipoprotein (HDL) (P = 0.049) on the first postoperative day and directly correlated with triglyceride levels on the second postoperative day (P = 0.017). Blood glucose levels were found to be increased on the first postoperative day (P = 0.021) and a correlation was detected between WBC count on the fourth postoperative day and doses of ascorbic acid and α-tocopherol (P = 0.027).. Suppression of the systemic inflammatory response to CPB is a double-edged sword and whether this suppression aids in the attenuation of morbidity and mortality is obscure. In this respect, ascorbic acid and α-tocopherol seem to display some anti-inflammatory effect, but further studies are necessary to reveal the actual therapeutic potential and the complex mechanism related to biochemical and inflammatory parameters.

Topics: Adult; Aged; alpha-Tocopherol; Analysis of Variance; Anti-Inflammatory Agents; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Inflammation; Inflammation Mediators; Leukocyte Count; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Retrospective Studies; Time Factors; Treatment Outcome; Triglycerides

The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity.. The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor α (TNFα), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress.. The mean body mass index (kg/m 2 ) in NAFLD patients, CHB, and HC were 26.4±3.7, 21.3±2.3, and 22.3±2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects.. Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.

Topics: Adipokines; Adult; Ascorbic Acid; Cytokines; Fatty Liver; Female; Hepatitis B, Chronic; Humans; India; Inflammation; Insulin; Insulin Resistance; Lipid Peroxidation; Liver; Male; Malondialdehyde; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Statistics as Topic; Superoxide Dismutase

An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients.. 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests.. According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments.. The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients. Our results suggest that further investigations into the use of IVC to reduce inflammation in diseases where inflammation is relevant are warranted.

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Inflammation; Neoplasms

Cardiovascular disease (CVD) remains one of the major killers in modern society. One strong risk factor of CVD is cigarette smoking that causes myocardial injury and leads to the genesis of pathological cardiovascular events. However, the exact toxic component(s) of cigarette smoke (CS) and its molecular and cellular mechanisms for causing myocardial injury leading to heart damage and its prevention are largely unknown.. Using a guinea pig model, here we show that chronic exposure to CS produces myocardial injury that is prevented by vitamin C. Male guinea pigs were fed either vitamin C-deficient (0.5 mg/day) or vitamin C-sufficient (15 mg/day) diet and subjected to CS exposure from 5 Kentucky Research cigarettes (3R4F)/day (6 days/week) in a smoke chamber up to 8 weeks. Pair-fed sham controls were subjected to air exposure instead of CS exposure under similar conditions. Myocardial injury was produced in CS-exposed marginal vitamin C-deficient guinea pigs as evidenced by release of cardiac Troponin-T and I in the serum, oxidative stress, inflammation, apoptosis, thrombosis and collagen deposition in the myocardium. Treatment of rat cardiomyocyte cells (H9c2) in vitro and guinea pigs in vivo with p-benzoquinone (p-BQ) in amounts derived from CS revealed that p-BQ was a major factor responsible for CS-induced myocardial damage. A moderately large dose of vitamin C (15 mg/day) prevented CS/p-BQ-induced myocardial injury. Population based studies indicated that plasma vitamin C levels of smokers without disease were significantly lower (p = 0,0000) than that of non-smokers. Vitamin C levels of CS-related cardiovascular patients were further lower (p = 0.0000) than that of smokers without disease.. The results indicate that dietary supplementation of vitamin C may be a novel and simple therapy for the prevention of pathological cardiovascular events in habitual smokers.

Topics: Adult; Aged; Animals; Apoptosis; Ascorbic Acid; Benzoquinones; Disease Progression; Enzyme Activation; Guinea Pigs; Humans; Inflammation; Male; Matrix Metalloproteinases; Middle Aged; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Neutrophil Infiltration; Oxidative Stress; Rats; Smoking

The aim of this study was to investigate a new flavone triglycoside, together with eleven phenolic metabolites from 80% aqueous methanol extract of S. splendens leaves (AME) and assessment of its hypoglycemic and antiinflammatory activities along with in vitro antioxidant effect.. The phenolic composition of S. splendens leaves was analyzed using UV, 1D and 2D NMR and negative ESI-MS spectroscopy. Hypoglycemic activity of AME was assessed by measuring blood glucose in streptozotocin induced-diabetic rats. Antiinflammatory activity was evaluated using the carrageenan-induced paw oedema test. Antioxidant activity was evaluated in vitro using DPPH test..  Twelve phenolic metabolites including three phenolic acids, namely caffeic acid 1, rosmarinic acid 2 and methyl rosmarinate 3; four flavone glycosides viz the new compound luteolin 7-O-(4″,6″-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside 4, apigenin 7-O-β-D-rutinoside 5, cosmosiin 6 and cinaroside 7, together with four flavones aglycone, luteolin 8, apigenin 9, pedalitin 10 and crisiliol 11 in addition to one coumarin, 6,7-dihydroxycoumarin 12 were isolated from the leaves of S. splendens Sellow ex Roem & Schult. The AME of S. splendens was non toxic to mice up to 5 g/kg b.wt. it exhibited a significant hypoglycemic activity at 250 and 500 mg/kg as compared with control pre-drug (zero time) for each group as well as the diabetic control. Moreover, AME exhibited a significant antiinflammatory activity only at 1000 mg/kg in comparison to indomethacin. Finally, AME exhibited a marked significant scavenging activity against DPPH; the maximum reactive reaction rate after 5 min was 62.9, 82.5, 83.7, 84.3 and 85.1% for the concentrations 10, 20, 30, 40 and 50 mg/ml, respectively in comparison to L-ascorbic acid (86.8%)..  This is the first study reporting the identification of a new flavone triglycoside, along with eleven known phenolic metabolites from AME of S. splendens. It showed significant hypoglycemic and antiinflammatory effects in dose dependant manner. Moreover it showed an in vitro antioxidant activity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hypoglycemic Agents; Indomethacin; Inflammation; Magnetic Resonance Spectroscopy; Male; Mice; Plant Extracts; Plant Leaves; Polyphenols; Rats; Rats, Sprague-Dawley; Salvia; Spectrometry, Mass, Electrospray Ionization

A series of novel acrylic acid derivatives bearing at the 3 position thienyl, furfuryl and 3,5-ditert-butyl-4-hydroxyphenyl substituents have been designed, synthesized and tested as potential dual lipoxygenase/cyclooxygenase-1 (LOX/COX-1) inhibitors and as antioxidant and anti-inflammatory agents. Some compounds have shown moderate antioxidant and COX-1 inhibitory activities, very good anti-inflammatory activity and an inhibition of soybean lipoxygenase (LOX) higher than caffeic acid. In particular, compound 4I disclosed a moderate in vitro LOX inhibition with an IC(50) = 100 μM whereas compounds 1I and 2II exhibited the best, albeit poor, activity as COX-1 inhibition (75% inhibition at 100 μM). Good radical scavenging properties were shown by compounds 4I, 3I and 1II. Docking simulations performed on LOX inhibitor 4I and COX-1 inhibitor 1I indicated that hydrophobic key interactions may govern the enzyme-inhibitor binding.

Topics: Acrylates; Animals; Anti-Inflammatory Agents; Antioxidants; Binding Sites; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Drug Design; Female; Free Radical Scavengers; Glycine max; Inflammation; Lipoxygenase; Lipoxygenase Inhibitors; Male; Models, Molecular; Protein Conformation; Rats

Phosphate ester of vitamin C and vitamin E (EPCK1), a strong antioxidant, is a water- and lipid-soluble phosphate ester of vitamin C and vitamin E. In the current study, we tested whether EPCK1 inhibits oxidative stress and prevents systemic inflammation.. Mice were randomly divided into a negative control group, a lipopolysaccharide (LPS)-induced sepsis group, and a group treated with an intraperitoneal infusion of EPCK1 (10 mg/kg) prior to or following LPS administration. In addition, RAW 264.7 cells were treated with LPS in the presence or absence of EPCK1. We examined levels of high mobility group box 1 (HMGB1) protein and inducible nitric oxide synthase (iNOS) in both in vivo and in vitro experiments, and liver histopathology in the in vivo experiment.. Liver histopathology significantly improved in the EPCK1 group compared with the LPS group. Although LPS administration increased HMGB1 and nitric oxide (NO) secretion, EPCK1 decreased the secretion of these mediators in vitro and in vivo.. Our findings suggest that EPCK1 may inhibit inflammation and potentially function as a novel anti-inflammatory therapeutic agent.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Cell Line; Disease Models, Animal; Esters; HMGB1 Protein; Inflammation; Lipopolysaccharides; Liver; Macrophages; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Phosphates; Sepsis; Survival Rate; Vitamin E

We evaluated the relationship of the plasma copper/zinc (Cu/Zn) ratio with nutritional status, inflammation, oxidative stress, and immune function in peritoneal dialysis patients.. Clinical and laboratory parameters were measured in patients (n=45) and age- and sex-matched healthy individuals (n=30).. There were significant negative correlations of the Cu/Zn ratio with nutrition-related parameters (body mass index [BMI], creatinine, hemoglobin, and albumin) and antioxidant (vitamin C and E) levels and positive correlations of the Cu/Zn ratio with the levels of high sensitivity C-reactive protein (hs-CRP) and oxidation products (malondialdehyde [MDA] and protein carbonyl). The Cu/Zn ratio was negatively correlated with the percentages of B- and T-lymphocyte subsets and the ratio of CD4/CD8 antigens.. In peritoneal dialysis patients, elevated Cu/Zn ratios are associated with malnutrition, increased oxidative stress, inflammation, and disrupted immune status.

Topics: Albumins; Ascorbic Acid; B-Lymphocyte Subsets; Biomarkers; Body Mass Index; C-Reactive Protein; Case-Control Studies; CD4-CD8 Ratio; Copper; Creatinine; Female; Hemoglobins; Humans; Immunity; Inflammation; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; T-Lymphocyte Subsets; Taiwan; Vitamin E; Zinc

This study was conducted to evaluate blood concentrations of inflammatory cytokines and oxidative stress-related biomarkers as risk factors of breast cancer and to determine the relation between these markers and antioxidant nutrient intake.. Study subjects were 134 patients with breast cancer and 149 controls. Total antioxidant capacity and concentrations of 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, interleukin (IL)-1β, IL-6, and IL-8 of blood samples were determined. A food-frequency questionnaire was used to assess nutrient intake.. Patients with breast cancer had significantly higher blood levels of oxidative stress markers compared with control subjects. Plasma concentrations of IL-1β and IL-6 were significantly higher in patients with breast cancer compared with those of control subjects. In the pooled analysis, total antioxidant capacity was significantly decreased with increasing quartiles of carbohydrate intake but was increased with increasing quartiles of total vitamin A intake and vitamin C intake. In addition, 8-hydroxy-2'-deoxyguanosine concentration was decreased with increasing quartiles of vitamin A and β-carotene. No significant association was found between nutrient intake and cytokine concentrations.. These results suggest that oxidative stress and inflammation may be associated with the risk of breast cancer. Total vitamin A intake was negatively related to oxidative stresses, possibly modifying the risk of breast cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Breast Neoplasms; Case-Control Studies; Deoxyguanosine; Diet; Diet Surveys; Dietary Carbohydrates; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Middle Aged; Oxidative Stress; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamins

Vitamin C supplementation has been suggested to reduce cardiovascular disease risk. However, no studies have examined the relationship between vitamin C status and vascular dysfunction in lean and obese individuals in the absence of supplementation. We examined whether vascular function is interrelated with vitamin C status and inflammation in healthy, college-aged lean and obese men with no history of dietary supplementation. A cross-sectional study was conducted during winter 2008 in lean and obese men aged 21±3 years (n=8/group). Brachial artery flow-mediated dilation (FMD) was measured to determine vascular endothelial function. Plasma antioxidants (vitamin C, vitamin E, and thiols), inflammatory proteins (C-reactive protein [CRP], myeloperoxidase [MPO], and cytokines), and cellular adhesion molecules were measured. Participants also completed 3-day food records on the days preceding their vascular testing. Group differences were evaluated by t tests, and correlation coefficients were determined by linear regression. FMD was 21% lower (P<0.05) in obese men. They also had 51% lower vitamin C intakes and 38% lower plasma vitamin C concentrations. Obese men had greater plasma concentrations of CRP, MPO, inflammatory cytokines, and cellular adhesion molecules. Participants' CRP and MPO were each inversely related (P<0.05) to FMD (r=-0.528 and -0.625) and plasma vitamin C (r=-0.646 and -0.701). These data suggest that low vitamin C status is associated with proinflammatory responses and impaired vascular function in lean and obese men. Additional study is warranted to determine whether improving dietary vitamin C intakes from food attenuate vascular dysfunction.

Topics: Antioxidants; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; C-Reactive Protein; Cell Adhesion Molecules; Cross-Sectional Studies; Cytokines; Endothelium, Vascular; Humans; Inflammation; Male; Nutritional Status; Obesity; Peroxidase; Thinness; Ultrasonography; Vitamin E; Young Adult

Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.. In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).. Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.. The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Comorbidity; Cross-Sectional Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis; Prealbumin; Prevalence; Renal Dialysis; Severity of Illness Index

The aims of the study were to test the susceptibility of THP-1 macrophages to develop oxidative stress and to deploy antioxidant defense mechanisms that insure the balance between the pro- and antioxidant molecules.. Differentiated THP-1 were incubated in the presence or absence of iron-ascorbate (Fe/As) (100/1000μM) and the antioxidants Trolox, BHT, α-Tocopherol and NAC.. Fe/As promoted the production of lipid peroxidation as reflected by the formation of malondialdehyde and H(2)O(2) along with reduced PUFA levels and elevated glutathione disulfide/total glutathione ratio, a reliable index of cellular redox status. THP-1 macrophages developed an increase in cytoplasmic SOD activity due in part to high cytoplasmic SOD1. On the other hand, a decline was noted in mRNA and protein of extra-cellular SOD3, as well as the activity of GSH-peroxidase, GSH-transferase and ATOX-1 expression.. Macrophages activated under conditions of oxidative stress do not adequately deploy a powerful endogenous antioxidant response, a situation that can lead to an enhanced inflammatory response.

Topics: Antioxidants; Ascorbic Acid; Cell Line; Dietary Supplements; Extracellular Space; Fatty Acids; Glutathione Disulfide; Humans; Hydrogen Peroxide; Inflammation; Iron; Lipid Peroxidation; Macrophages; Malondialdehyde; Models, Biological; Oxidation-Reduction; Oxidative Stress; Tumor Necrosis Factor-alpha

Acetyl-L-carnitine (ALCAR) has been shown to prevent experimental selenite cataractogenesis, a manifestation of oxidative stress, but little is known about its potential in other settings of oxidative stress. The present study was based on the hypothesis that ALCAR prevents carbon tetrachloride (CCl(4))-induced oxidative stress in vital tissues. Male albino Wistar rats were divided into three groups, each of six rats. Group I (control) rats received only vehicle (1 ml/kg b.w.) for 4 days; Group II (CCl(4)-exposed, untreated) rats received CCl(4) (2 ml/kg b.w.) on the second and third days and vehicle on the first and fourth days; Group III (CCl(4)-exposed, ALCAR-treated) rats received ALCAR (200 mg/kg b.w.) for 4 days and CCl(4) on the second and third days. All administrations were made intraperitoneally. After the experimental period, significantly (P < 0.05) elevated mean serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase were observed in Group II rats when compared to Group I and Group III rats. The mean levels of vitamin C, vitamin E, and reduced glutathione and the mean activities of superoxide dismutase, catalase, and glutathione peroxidase were significantly (P < 0.05) lower in samples of hemolysate and of liver, kidney, and brain tissues of Group II rats than those in Group I and Group III rats. The mean level of lipid peroxidation was significantly (P < 0.05) higher in Group II rats than that in Group I and Group III rats. Moreover, the CCl(4)-induced upregulation of inducible nitric oxide synthase expression was prevented by ALCAR in the liver and brain tissues. These results suggest that ALCAR is able to prevent the CCl(4)-induced oxidative stress.

Topics: Acetylcarnitine; Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Brain; Carbon Tetrachloride; Catalase; Glutathione; Glutathione Peroxidase; Inflammation; Injections, Intraperitoneal; Kidney; L-Lactate Dehydrogenase; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Serum; Superoxide Dismutase; Vitamin E

Genetic variation in complement factor H (CFH) has been implicated as a major risk factor for age-related macular degeneration (AMD). The reduction in CFH amount or its complement-modulating activity may lead to inadequate control of complement-driven inflammation at the outer retina. We explored the effect of photo-oxidative stress and inflammatory cytokine on the expression of CFH in retinal pigment epithelial (RPE) cells.. Cultured human RPE cells were exposed to blue light in the presence of interferon-γ (IFN-γ). CFH expression in cell lysate was examined by Western blot and the secretory CFH in culture medium was analyzed by ELISA. RPE cells were treated with vitamin C and exogenous superoxide dismutase mimetic (Tempol) before photo-oxidative treatments. The intracellular reactive oxygen species were examined by flow cytometry.. IFN-γ increased CFH expression in RPE and the expression was suppressed significantly under concomitant blue light illumination. The secretory CFH level also decreased significantly under blue light illumination, which was related to the decreased intracellular mRNA and protein expressions of CFH. The suppression was mediated through an oxidative mechanism, and was particularly related to superoxide anion generation. The suppression of CFH expression in RPE under blue light illumination was abrogated by vitamin C and Tempol.. Photo-oxidative stress reduces the ability of IFN-γ to increase CFH expression in RPE. Apart from reducing the oxidative damage, vitamin C reduces the suppression of CFH under photo-oxidative stress. These results suggest a new perspective of the interaction between oxidative stress and inflammation, and provide a potential novel treatment strategy for age-related macular degeneration.

Topics: Antioxidants; Ascorbic Acid; Blotting, Western; Cell Survival; Cells, Cultured; Complement Factor H; Cyclic N-Oxides; Cytokines; Follow-Up Studies; Gene Expression Regulation; Genetic Variation; Humans; Inflammation; Intracellular Fluid; Macular Degeneration; Oxidative Stress; Reactive Oxygen Species; Retinal Pigment Epithelium; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spin Labels

Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model.. Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2'-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage.. No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24).. Resuscitation with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

Topics: Animals; Antioxidants; Ascorbic Acid; Cytokines; Disease Models, Animal; DNA Damage; Enzyme-Linked Immunosorbent Assay; Inflammation; Multiple Trauma; Oxidative Stress; Plasma; Resuscitation; Shock, Hemorrhagic; Swine; Treatment Outcome

Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown.. Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals.. No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p < 0.05), but less so at 2 hours in the AA group compared with CA and HCl.. In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Female; Freeze Drying; Inflammation; Interleukin-6; Plasma; Polymerase Chain Reaction; Shock, Hemorrhagic; Swine; Tumor Necrosis Factor-alpha

The association between aluminum (Al), essential trace metals, oxidative stress, and inflammation status was evaluated in hemodialysis patients.. Biochemical parameters in blood were determined in long-term hemodialysis patients (n=69) and age- and sex-matched healthy individuals (n=30).. Compared with healthy subjects, patients had significantly higher concentrations of plasma Al. Elevated Al was negatively associated with the essential metals zinc, selenium, and iron. Al concentrations were strongly and positively correlated with contents of the oxidation products malondialdehyde and protein carbonyl. Inverse relationships were observed between Al concentrations and reduced concentrations of glutathione, β-carotene, vitamin C, and vitamin E. Patients were also observed to have significantly increased production values of plasma high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-5.. An increased plasma Al concentration is associated with disturbed concentrations of essential metals, increased oxidative stress, and increased inflammation status in hemodialysis patients.

Topics: Aluminum; Antioxidants; Ascorbic Acid; beta Carotene; C-Reactive Protein; Case-Control Studies; Female; Glutathione; Humans; Inflammation; Interleukin-5; Iron; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Renal Dialysis; Risk Factors; Selenium; Trace Elements; Tumor Necrosis Factor-alpha; Vitamin E; Zinc

Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.

Topics: Analgesics; Animals; Ascorbic Acid; Behavior, Animal; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Freund's Adjuvant; Ganglia, Spinal; Hyperalgesia; Inflammation; Injections, Spinal; Male; Mice; Mice, Inbred C57BL; Neuralgia; p38 Mitogen-Activated Protein Kinases; Peripheral Nerve Injuries; Phosphorylation; Reactive Oxygen Species; Spinal Cord; Time Factors; Vitamin E

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

To examine the association between concentrations of serum vitamin C, a contributive factor to prevention of cardiovascular disease and levels of hs-CRP, a risk factor for cardiovascular disease, in population-based samples of middle-aged men and women.. A cross-sectional study.. The subjects were 778 men and 1404 women, aged 40-69 years, who participated in a cardiovascular risk survey in Kyowa, Ibaraki prefecture in 2002 as part of the Circulatory Risk in Communities Study (CIRCS). Inverse associations between serum vitamin C concentrations and hs-CRP levels were established for both men and women. Multivariable-adjusted mean values of hs-CRP for the lowest to highest quintiles of vitamin C levels were 0.75, 0.65, 0.61, 0.61 and 0.47 mg/L (P for trend <0.001) for men, and 0.56, 0.51, 0.49, 0.41 and 0.41 mg/L (P for trend <0.001) for women. The inverse association between vitamin C and hs-CRP was stronger for non-smoking men and women, non-overweight women and postmenopausal women.. Serum vitamin C concentrations were found to be inversely associated with hs-CRP levels in both men and women, primarily among non-smokers, non-overweight women and postmenopausal women. The respective roles of serum vitamin C and hs-CRP levels in the development of cardiovascular disease thus warrant further investigation.

Topics: Adult; Aged; Ascorbic Acid; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Japan; Male; Middle Aged; Models, Statistical; Reference Values; Risk Factors; Sex Factors

Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Cytokines; Free Radical Scavengers; Heart; Inflammation; Kidney; Liver; Lung; Male; Mice; Multiple Organ Failure; Myocardium; Oxygen; Reactive Oxygen Species; Sepsis; Thiourea; Zymosan

Underlying cardiovascular disease (CVD) is a risk factor for the exacerbation of air pollution health effects. Pulmonary oxidative stress, inflammation, and altered iron (Fe) homeostasis secondary to CVD may influence mammalian susceptibility to air pollutants. Rodent models of CVD are increasingly used to examine mechanisms of variation in susceptibility. Baseline cardiac and pulmonary disease was characterized in healthy normotensive Wistar Kyoto (WKY) rats, cardiovascular compromised spontaneously hypertensive rats (SHR), and spontaneously hypertensive heart failure (SHHF) rats. Blood pressure, heart rate, and breathing frequencies were measured in rats 11 to 12 wk of age, followed by necropsy at 14 to 15 wk of age. Blood pressure and heart rate were increased in SHR and SHHF relative to WKY rats (SHR > SHHF > WKY). Increased breathing frequency in SHHF and SHR (SHR > SHHF > WKY) resulted in greater minute volume relative to WKY. Bronchoalveolar lavage fluid (BALF) protein and neutrophils were higher in SHHF and SHR relative to WKY (SHHF >> SHR > WKY). Lung ascorbate and glutathione levels were low in SHHF rats. BALF Fe-binding capacity was decreased in SHHF relative to WKY rats and was associated with increased transferrin (Trf) and ferritin. However, lung ferritin was lower and Trf was higher in SHHF relative to WKY or SHR rats. mRNA for markers of inflammation and oxidative stress (macrophage inflammatory protein [MIP]-2, interleukin [IL]-1alpha, and heme oxygenase [HO]-1) were greater in SHHF and SHR relative to WKY rats. Trf mRNA rose in SHR but not SHHF relative to WKY rats, whereas transferrin receptors 1 and 2 mRNA was lower in SHHF rats. Four of 12 WKY rats exhibited cardiac hypertrophy despite normal blood pressure, while demonstrating some of the pulmonary complications noted earlier. This study demonstrates that SHHF rats display greater underlying pulmonary complications such as oxidative stress, inflammation, and impaired Fe homeostasis than WKY or SHR rats, which may play a role in SHHF rats' increased susceptibility to air pollution.

Topics: Animals; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Cardiovascular Diseases; Disease Models, Animal; Ferritins; Gene Expression; Glutathione; Heart Failure; Hemodynamics; Homeostasis; Hypertension; Inflammation; Iron; Lung; Lung Diseases; Male; Obesity; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Respiratory Function Tests; Stroke; Transferrin

To investigate the possibility of reversing endothelial dysfunction and inflammation by glucose normalization, antioxidants and insulin per se, in different subgroups of Type 1 diabetic patients.. Three subgroups of Type 1 diabetic patients were studied: patients within 1 month of diagnosis (subgroup 1); patients with approximately 5 years' disease duration and with glycated haemoglobin (HbA(1c)) 7.0% since diagnosis (subgroup 3). Participants underwent four procedures: 2-h hyperglycaemic clamp followed by: (A) 12 h near-normalization of blood glucose, with the addition of vitamin C during the last 6 h; (B) 12-h vitamin C and near-normalization of blood glucose for the last 6 h; (C) both vitamin C and near-normalization of blood glucose for 12 h; (D) hyperglycaemic-hyperinsulinaemic clamp for 12 h, with the addition of vitamin C during the last 6 h.. After 2 h of hyperglycaemia, markers of endothelial dysfunction, nitrotyrosine, 8-iso prostaglandin F2alpha, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, interleukin (IL)-6 and IL-18 were increased in all the subgroups. Levels were normalized, at all time points, by treatments A, B and C in the subgroups 1 and 2. In the third subgroup, levels were normalized only by the simultaneous normalization of blood glucose and vitamin C treatment. During treatment D, the levels were improved at 6 h in all the subgroups, but normalized at 12 h only after vitamin C in subgroups 1 and 2, but not in subgroup 3.. This study suggests that different subgroups of Type 1 diabetic patients react identically to acute hyperglycaemia and insulin, but differently to glucose normalization.

Topics: Ascorbic Acid; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Male; Oxidative Stress; Young Adult

Exposure to air pollutants such as formaldehyde (FA) leads to inflammation, oxidative stress and immune-modulation in the airways and is associated with airway inflammatory disorders such as asthma. The purpose of our study was to investigate the effects of exposure to FA on the allergic lung inflammation. The hypothesized link between reactive oxygen species and the effects of FA was also studied. To do so, male Wistar rats were exposed to FA inhalation (1%, 90 min daily) for 3 days, and subsequently sensitized with ovalbumin (OVA)-alum by subcutaneous route. One week later the rats received another OVA-alum injection by the same route (booster). Two weeks later the rats were challenged with aerosolized OVA. The OVA challenge of rats upon FA exposure induced an elevated release of LTB 4, TXB 2, IL-1 beta, IL-6 and VEGF in lung cells, increased phagocytosis and lung vascular permeability, whereas the cell recruitment into lung was reduced. FA inhalation induced the oxidative burst and the nitration of proteins in the lung. Vitamins C, E and apocynin reduced the levels of LTB 4 in BAL-cultured cells of the FA and FA/OVA groups, but increased the cell influx into the lung of the FA/OVA rats. In OVA-challenged rats, the exposure to FA was associated to a reduced lung endothelial cells expression of intercellular cell adhesion molecule 1 (ICAM-1). In conclusion, our findings suggest that FA down regulate the cellular migration into the lungs after an allergic challenge and increase the ability of resident lung cells likely macrophages to generate inflammatory mediators, explaining the increased lung vascular permeability. Our data are indicative that the actions of FA involve mechanisms related to endothelium-leukocyte interactions and oxidative stress, as far as the deleterious effects of this air pollutant on airways are concerned.

Topics: Air Pollutants; Animals; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Capillary Permeability; Formaldehyde; Hypersensitivity; Inflammation; Lung; Lung Diseases; Male; Phagocytosis; Rats; Rats, Wistar; Respiratory Burst; Vitamin E

Increasing evidence indicates that disequilibrium of the alveolar oxidant-antioxidant balance may play a role in the pathogenesis of chronic fibrosing lung diseases. Excessive production of oxidants and a differential regulation of antioxidant enzymes have been described under these conditions. We characterized for the first time numerous nonenzymatic low-molecular-weight antioxidants in bronchoalveolar lavage fluids from patients with different forms of lung fibrosis initiated either by injury to the alveolar epithelium (idiopathic pulmonary fibrosis, IPF) or by inflammation (chronic sarcoidosis/hypersensitivity pneumonitis). Footprints of oxidative stress accompanied by an increase in the majority of antioxidants assessed were observed in all patient groups: elevated levels of uric acid, ascorbic acid, retinol, and alpha-tocopherol were noted, whereas glutathione levels were unchanged. The expression of Nrf2, an important redox-sensitive transcriptional regulator of antioxidants, was increased in IPF lungs. Our findings were corroborated in the bleomycin model of lung fibrosis where--aside from uric acid--nonenzymatic antioxidants were elevated during the fibrotic phase. In conclusion, alveolar levels of nonenzymatic antioxidants are elevated in fibrosing lung diseases, but are incapable of restoring oxidative balance. This increase may be part of an adaptive response to oxidative stress. However, a leakage from the blood may also contribute to our findings.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Bronchoalveolar Lavage Fluid; Glutathione; Humans; Idiopathic Pulmonary Fibrosis; Immunohistochemistry; Inflammation; Lung Diseases, Interstitial; Oxidative Stress; Pulmonary Fibrosis; Rabbits; Uric Acid; Vitamin A

Fruit and vegetable consumption has been associated with a reduced risk of several diseases including CVD. A part of these effects seen could be linked to anti-inflammatory and antioxidative effects, although this has not been thoroughly investigated. The present study was designed to investigate the effects of the dietary intake of beta-carotene, alpha-tocopherol and ascorbic acid on in vivo biomarkers of inflammation (PGF2alpha, high-sensitive C-reactive protein (hsCRP) and IL-6 formation) and oxidative stress (F2-isoprostane formation), the two important factors associated with accelerated atherosclerosis. The dietary intake of 704 participants in the Uppsala Longitudinal Study of Adult Men (ULSAM) at age 70 years was registered and inflammatory and oxidative stress biomarkers were quantified 7 years later. The registered dietary intakes of ascorbic acid and alpha-tocopherol were negatively associated linearly and in quartiles with both PGF2alpha, hsCRP, IL-6 and F2-isoprostanes, where ascorbic acid intake generally was more strongly associated. Dietary intake of beta-carotene was only significantly negatively associated with F2-isoprostanes. In conclusion, the present study is the first to suggest that the intake of food rich in antioxidants is associated with reduced cyclo-oxygenase- and cytokine-mediated inflammation and oxidative stress at 7 years of follow-up. These associations could be linked to the beneficial effects of fruit and vegetables observed on CVD.

Topics: Aged; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers; C-Reactive Protein; Creatinine; Diet; Dinoprost; Humans; Inflammation; Interleukin-6; Linear Models; Longitudinal Studies; Male; Oxidative Stress; Vitamins

The protective role of diallyl sulfide (DAS) in attenuating gentamicin-induced nephrotoxicity has been reported earlier. However, the mechanism of induction of antioxidants by DAS in nephrotoxicity remains elusive. This study is aimed to elucidate the role of a transcription factor, Nuclear factor E2-related factor 2 (Nrf2) in inducing antioxidants and phase II enzymes during gentamicin toxicity in Wistar rats. DAS was administered intraperitoneally at a dosage of 150 mg/kg body weight once daily for 6 days. Gentamicin was administered intraperitoneally at a dosage of 100 mg/kg body weight, once daily for 6 days. Gentamicin-induced rats showed a significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon treatment with DAS. A significant increase in kidney myeloperoxidase (MPO) and lipid peroxidation (LPO) levels was observed in gentamicin-induced rats, which was reduced upon treatment with DAS. Gentamicin-induced rats also showed a significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) in rat kidney, which was increased upon treatment with DAS. Immunohistochemical studies in gentamicin-induced rats demonstrated a marked increase in the immunoreactivity of inducible nitric oxide synthase (iNOS), nuclear transcription factor (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha) that were reduced after treatment with DAS. Further, the involvement of Nrf2 in antioxidant induction was analyzed by Western blot and immunofluorescence. To conclude, DAS enhances antioxidants and suppresses inflammatory cytokines through the activation of Nrf2, thereby protecting the cell against oxidative stress induced by gentamicin.

Topics: Allyl Compounds; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Biomarkers; Enzyme Induction; Gentamicins; Glutathione; Inflammation; Kidney; Kidney Glomerulus; Kidney Tubules; Lipid Peroxidation; Male; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Sulfides; Tumor Necrosis Factor-alpha; Vitamin E

Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder characterized by sphingolipid and cholesterol storage in the late endocytic system. In common with other neurodegenerative diseases, activation of the innate immune system occurs in the brain resulting in neuro-inflammation. Targeting inflammation in the brain therefore represents a potential clinical intervention strategy that aims to slow the rate of disease progression and improve quality of life. We evaluated non-steroidal anti-inflammatory drugs (NSAIDs) and an anti-oxidant to determine whether these agents are disease modifying in an acute mouse model of NPC1. NSAIDs significantly prolonged the lifespan of NPC1 mice and slowed the onset of clinical signs. However, anti-oxidant therapy was of no significant benefit. Combining NSAID therapy with substrate reduction therapy (SRT) resulted in additive benefit. These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Brain; Disease Models, Animal; Inflammation; Mice; Mice, Inbred BALB C; Mice, Knockout; Niemann-Pick Disease, Type C

The present study was designed to investigate the antioxidant, anti-inflammatory and analgesic potential of Citrus decumana peel extract. Antioxidant activity of Citrus decumana peel extract in four solvent systems was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH(.)) and hydrogen peroxide (H(2)O(2)) radical scavenging methods. Ethyl acetate peel extract of Citrus decumana (EtCD) was studied for its anti-inflammatory and analgesic activities at a dose level of 100, 200 and 300 mg/kg. Anti-inflammatory activity was performed using carrageenan-induced paw edema in rats. Analgesic activity was evaluated for its central and peripheral pharmacological actions in mice. EtCD showed significant antioxidant activity in a dose-dependent manner when compared with ascorbic acid. EtCD at the dose of 300 mg/kg produced significant decrease in paw volume and pain when compared with reference drug diclofenac and morphine, respectively. The Citrus decumana peel extract may be useful as a natural antioxidant in the treatment of inflammation and pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Citrus; Diclofenac; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Inflammation; Male; Mice; Morphine; Pain; Plant Extracts; Rats; Rats, Wistar; Solvents

The Ca(2+)-ATPase of the sarcoplasmic reticulum (SERCA) of rabbit skeletal muscle was oxidized by Fe2+/H2O2/ascorbic acid (AA), a system which generates HO(.) radicals according to the Fenton reaction: (Fe2(+)+H2O2-->HO(.)+OH(-)+Fe(3+)) under conditions similar to the pathological state of inflammation. Under these conditions, when hydroxyl-radicals and/or ferryl-radicals are generated, a 50% decrease of the SERCA activity was observed, a significant decrease of SH groups and an increase of protein carbonyl groups and lipid peroxidation were identified. Two new bands, time dependent in density, appeared in the SERCA protein electrophoresis after incubation with the Fenton system (at approximately 50 and 75kDa), probably due to structural changes as supported also by trypsin digestion. Immunoblotting of DNPH derivatized protein bound carbonyls detected a time dependent increase after incubation of SERCA with the Fenton system. Trolox and the pyridoindole stobadine (50microM) protected SR against oxidation induced via the Fenton system by preventing SH group oxidation and lipid peroxidation. Pycnogenol((R)) and EGb761 (40microg/ml) protected SERCA in addition against protein bound carbonyl formation. In spite of the antioxidant effects, trolox and stobadine were not able to prevent a decrease in the SERCA Ca(2+)-ATPase activity. Pycnogenol and EGb761 even enhanced the decrease of the Ca(2+)-ATPase activity induced by the Fenton system, probably by secondary oxidative reactions.

Topics: Animals; Antioxidants; Ascorbic Acid; Carbolines; Chromans; Ferrous Compounds; Flavonoids; Ginkgo biloba; Hydrogen Peroxide; Inflammation; Lipid Peroxidation; Muscle, Skeletal; Oxidation-Reduction; Plant Extracts; Protein Carbonylation; Rabbits; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine; Time Factors

Topics: Animals; Antioxidants; Ascorbic Acid; Chronic Disease; Clinical Trials as Topic; Complementary Therapies; Flavonoids; Humans; Inflammation; Liver Diseases; Phenols; Polyphenols; Reactive Oxygen Species; Reproducibility of Results; Tea; Treatment Outcome; Vitamin A; Vitamin E

Fast food is high in energy density and low in essential micronutrient density, especially zinc (Zn), of which antioxidant processes are dependent. We have tested the hypothesis that frequent fast food consumption could induce oxidative damage associated with inflammation in weanling male rats in relevance to Zn deprivation, which could adversely affect testis function. Zn and iron (in plasma and testicular tissue), plasma antioxidant vitamins (A, E, and C), as well as testicular superoxide dismutase (SOD) and reduced glutathione (GSH), lipid peroxidation indexes (thiobarbituric acid reactive substances (TBARS) and lipoprotein oxidation susceptibility (LOS)), and inflammatory markers (plasma C-reactive protein (CRP) and testicular tumour necrosis factor-alpha (TNF-alpha)) were determined. Serum testosterone and histological examination of the testis were performed also. We found a severe decrease in antioxidant vitamins and Zn, with concomitant iron accumulation. Zinc deficiency correlated positively with SOD, GSH, antioxidant vitamins and testosterone, and negatively with TBARS, LOS, CRP and TNF-alpha, demonstrating a state of oxidative stress and inflammation. We concluded that micronutrient deficiency, especially Zn, enhanced oxidative stress and inflammation in testicular tissue leading to underdevelopment of testis and decreased testosterone levels.

Topics: Animals; Antioxidants; Ascorbic Acid; Deficiency Diseases; Feeding Behavior; Inflammation; Iron; Male; Micronutrients; Nutritional Requirements; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Testis; Testosterone; Vitamin A; Vitamin E; Zinc

Topics: Acetylcysteine; Acute Kidney Injury; Antioxidants; Ascorbic Acid; Biomarkers; Cell Death; Cell Hypoxia; Consensus; Contrast Media; Creatinine; Epithelial Cells; Fluid Therapy; Humans; Inflammation; Infusions, Intravenous; Kidney Tubules; Multicenter Studies as Topic; Oxidative Stress; Practice Guidelines as Topic; Protective Agents; Randomized Controlled Trials as Topic; Renal Circulation; Treatment Outcome

Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls.. Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile].. Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease.. This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.

Topics: Adult; Antioxidants; Ascorbic Acid; Body Mass Index; C-Reactive Protein; Carotenoids; Case-Control Studies; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Inflammation; Inflammatory Bowel Diseases; Male; Nutritional Status; Oxidation-Reduction; Surveys and Questionnaires; Vitamin E; Vitamins

It is well-known that parapneumonic effusions lead to the formation of inflammatory exudates which contain an increasing amount of inflammatory cells, especially polymorphonuclear. At these pathological conditions characterized by oxidative stress, ascorbic acid (AA) plays an important role in quenching free radicals, so that it could protect neutrophils and mesothelial cells from oxidative damage. Besides that ascorbic acid and its metabolite dehydroascorbic acid (DHA) alters the sheep visceral and parietal pleura permeability. More specific ascorbic acid as well as dehydroascorbic acid decreases the permeability of pleura after addition on apical and basolateral side in both visceral and parietal pleurae. It seems that, AA and DHA have an opposite action upon pleura from that of the inflammatory mediators, like VEGF, which increases the permeability of pleura and causes mesothelial barrier dysfunction. The decrease of pleura permeability induced by AA and DHA suggest the hypothesis that AA and/or its metabolite DHA during inflammatory reactions not only protects mesothelial cells from oxidative damage, but also contributes to maintaining the mesothelial barrier function. Consequently, the inflammatory pleural fluid may be trapped in pleural space and the inflammation may be restricted, and have extension avoided.

Topics: Animals; Ascorbic Acid; Cytoplasm; Dehydroascorbic Acid; Epithelium; Humans; Inflammation; Models, Biological; Oxidative Stress; Oxygen; Phagocytosis; Pleura; Sheep; Vascular Endothelial Growth Factor A

Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities.. Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring.. Esophagitis was present in all 63 animals completing the study and severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups.. In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Esophagitis, Peptic; Esophagus; Female; Inflammation; Jejunum; Lactones; Models, Animal; Random Allocation; Rats; Rats, Wistar; Sulfones; Ulcer

It has been reported that apelin functions as an adipokine, which has been associated to obesity and insulin resistance. The objective of this study was to analyze the apelin mRNA expression in white adipose tissue (WAT) from high-fat (Cafeteria) fed rats, in order to examine potential relationships with obesity markers and other related risk factors. Animals fed on the high-fat diet during 56 days increased their body weight, total body fat and WAT depots weights when compared to controls. Apelin subcutaneous mRNA expression was higher in the Cafeteria than in the Control fed group and this increase was partially reversed by dietary vitamin C supplementation. Statistically significant associations between subcutaneous apelin gene expression and almost all the studied variables were identified, being of special interest the correlations found with serum leptin (r=0.517), liver malondialdehyde (MDA) levels (r=0.477), and leptin, IRS-3 and IL-1ra retroperitoneal mRNA expression (r=0.701; r=0.692 and r=0.561, respectively). These associations evidence a possible role for apelin in the excessive weight gain induced by high-fat feeding and increased adiposity, insulin-resistance, liver oxidative stress and inflammation.

Topics: Adiposity; Animals; Apelin; Ascorbic Acid; Biomarkers; Carrier Proteins; Diet, Atherogenic; Inflammation; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Intra-Abdominal Fat; Leptin; Liver; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Subcutaneous Fat

The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Ascorbic Acid; Blood Pressure; Chemokine CCL2; Disease Models, Animal; Glomerular Filtration Rate; Glutathione; Heart Rate; Hydrogen Peroxide; Hypertension; Inflammation; Interleukin-6; Kidney; Macrophages; Monocytes; NF-kappa B; Oxidative Stress; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; Sodium Chloride, Dietary; Superoxides; Time Factors; Tumor Necrosis Factor-alpha; Vitamin E

UV light is considered one of the major etiological factor in skin aging, cancer and also to systemic impairment such as immunosuppression. Increased production of reactive oxygen species (ROS) and oxidative stress condition are known to play a central role in initiating and driving the signalling events that lead to cellular response following UV irradiation. In the present study we have investigated the photoprotective activity of a standardized extract from red orange (ROE), obtained from three red orange varieties and containing as main active principles phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) and ascorbic acid. The aim of this study was to evaluate the efficacy of ROE in modulating cellular responses to UVB in human keratinocytes (HaCaT). Our data indicate that ROE is potentially able to efficiently counteract UVB-induced response, and in particular some events associated to inflammation and apoptosis, such as NF-kB and AP-1 translocation and procaspase-3 cleavage. This activity is probably due to a block of cellular oxidative stress-related events. Thus we can propose ROE as a useful natural standardised extract in skin photoprotection with promising applications in the field of dermatology.

Topics: Anthocyanins; Apoptosis; Ascorbic Acid; Blotting, Western; Cell Line, Transformed; Citrus sinensis; Coumaric Acids; Electrophoretic Mobility Shift Assay; Flavanones; Fruit; Humans; Inflammation; Keratinocytes; Phytotherapy; Plant Extracts; Ultraviolet Rays

To evaluate the states of inflammation, oxidative stress and carbonyl stress in uremic patients and analyze their relationships.. One hundred and twenty-eight cases were divided into 6 groups: non-dialysis uremia group (n=25), peritoneal dialysis group (n=19), hemophan(Hem) membrane dialysis group (n=25), polyamide (PS) membrane dialysis group (n=25), diabetes with normal renal function group (n= 23) and normal control group (n=11). Spectrophotometry and immune turbidimetry were used to measure the serum SOD, VitC, VitE, MDA and total carbonyl compounds (TCC) levels.. Compared with non-uremia groups, the uremia groups had lower serum SOD, VitE and VitC levels, but higher CRP, MDA and TCC levels (P < 0.01). The peritoneal dialysis group had higher SOD, VitC, VitE levels in comparison with the Hem group, but did not differ from PS group in those levels (P > 0.05). The MDA and TCC levels in the peritoneal dialysis group were lower than those in the two hemodialysis groups, but there were no significant differences in CRP level between the groups. Compared with Hem group, the PS group had higher VitC, VitE levels, higher TCC clearance, and the same SOD, MDA, CRP and pre-dialysis TCC levels. When the variables were analyzed with TCC, the results of multi-variate regression showed that the standardized coefficients were MDA (0.727, P < 0.01), CRP (0.370, P < 0.01), SOD (0.192, P < 0.05), VitC (-0.153, P < 0.01), VitE (0.054, P = 0.30) respectively.. Uremic patients are in inflammatory, oxidative-stress and carbonyl-stress states. Inflammation and oxidative stress are probably the important mechanism of carbonyl stress. It is not yet clear whether dialysis methods can influence uremic inflammatory, oxidative-stress or carbonyl-stress state.

Topics: Adult; Ascorbic Acid; C-Reactive Protein; Female; Glycation End Products, Advanced; Humans; Inflammation; Male; Malondialdehyde; Middle Aged; Nephelometry and Turbidimetry; Oxidative Stress; Protein Carbonylation; Renal Dialysis; Spectrophotometry; Superoxide Dismutase; Uremia; Vitamin E

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Topics: Animals; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cadmium; Dinoprost; Glutathione; Inflammation; Lung; Macrophages; Male; Neutrophils; Oxidation-Reduction; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Sprague-Dawley; Uric Acid

Topics: Antioxidants; Ascorbic Acid; Atherosclerosis; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Oxidants; Oxidative Stress; Renal Dialysis

It has been suggested that a high dietary intake and high circulating concentrations of vitamin C may protect against ischemic heart disease.. The objective was to examine the associations between dietary and plasma vitamin C concentrations, fruit and vegetable intakes, and markers of inflammation and hemostasis associated with cardiovascular disease in older men free of cardiovascular disease.. This cross-sectional study examined 3258 men aged 60-79 y with no physician diagnosis of myocardial infarction, stroke, or diabetes and who were drawn from general practices in 24 British towns. Fruit and vegetable intakes and dietary vitamin C were assessed by using a food-frequency questionnaire.. Plasma vitamin C, fruit intake, and dietary vitamin C intake were significantly and inversely associated with mean concentrations of C-reactive protein, an acute phase reactant, and tissue plasminogen activator (t-PA) antigen, a marker of endothelial dysfunction, even after adjustment for confounders. Vegetable intake was correlated significantly (inversely) only with t-PA. For plasma vitamin C (highest versus lowest quartile), the adjusted odds of elevated C-reactive protein and t-PA (highest tertile versus lowest tertile) were 0.56 (95% CI: 0.44, 0.71) and 0.79 (0.62, 1.00); for fruit intake, the corresponding odds ratios were 0.76 (0.60, 0.95) and 0.76 (0.61, 0.95). Plasma (but not dietary) vitamin C also showed inverse associations with both fibrinogen concentrations and blood viscosity. No associations were seen with von Willebrand factor or factor VIII.. The findings suggest that vitamin C has antiinflammatory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Topics: Acute-Phase Proteins; Aged; Antioxidants; Ascorbic Acid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Confidence Intervals; Cross-Sectional Studies; Endothelium, Vascular; Fruit; Hemostasis; Humans; Inflammation; Life Style; Male; Middle Aged; Odds Ratio; Surveys and Questionnaires; Tissue Plasminogen Activator; United Kingdom; Vegetables; von Willebrand Factor

The observation that antioxidant vitamins fail to confer protective benefits in large, well-designed randomized clinical trials has led many to question the role of oxidative stress in the pathogenesis of disease. However, there is little evidence that proposed antioxidants actually scavenge reactive intermediates in vivo. Ascorbate reacts rapidly with oxidants produced by activated neutrophils in vitro, and neutrophils markedly increase their oxidant production when mice are infected intraperitoneally with the gram-negative bacterium Klebsiella pneumoniae. To explore the antioxidant properties of ascorbate in vivo, we therefore used K. pneumoniae infection as a model of oxidative stress. When mice deficient in L-gulono-gamma-lactone oxidase (Gulo(-/-)), the rate-limiting enzyme in ascorbate synthesis, were depleted of ascorbate and infected with K. pneumoniae, they were three times as likely as ascorbate-replete Gulo(-/-)mice to die from infection. Mass spectrometric analysis of peritoneal lavage fluid revealed a marked increase in the levels of oxidized amino acids and of F2-isoprostanes (sensitive and specific markers of lipid oxidation) in infected animals. Surprisingly, there were no significant differences in the levels of the oxidation products in the ascorbate-deficient and -replete Gulo(-/-)mice. Our observations suggest that ascorbate plays a previously unappreciated role in host defense mechanisms against invading pathogens but that the vitamin does not protect amino acids and lipids from oxidative damage during acute inflammation. To examine the oxidation hypothesis of disease, optimal antioxidant regimens that block oxidative reactions in animals and humans need to be identified.

Topics: Amino Acids; Animals; Antioxidants; Ascorbic Acid; Inflammation; Klebsiella Infections; Klebsiella pneumoniae; L-Gulonolactone Oxidase; Lipid Peroxidation; Mice; Mice, Knockout; Oxidation-Reduction; Sepsis

Alzheimer's disease is characterized by extracellular beta-amyloid plaques, intraneuronal Tau-inclusions and cell death of cholinergic neurons. Recent evidence indicates that the vascular system may play an important role in the development of this progressive neurodegenerative disease. The aim of this study was to observe, if brain capillary endothelial cells (BCEC) may produce and secrete factors which induce cell death of cholinergic neurons, and if this effect is counteracted by (1) NGF, MK-801 or vitamin C, (2) modulated by experimentally-induced inflammation with interleukin-1beta and lipopolysaccharide (IL-1beta and LPS) or (3) by blocking of different intracellular signalling pathways. Cholinergic neurons were cultivated in organotypic brain slices of the nucleus basalis of Meynert and treated with conditioned medium derived from BCEC, supplemented with different protective factors. BCEC were stimulated with IL-1beta and LPS or different intracellular pathway inhibitors before collection of conditioned medium. Cholinergic neurons were detected by immunohistochemistry for choline-acetyltransferase. Possible effects on BCEC viability and proliferation were determined by nuclear staining, BrdU incorporation and release of nitrite and lactate-dehydrogenase. BCEC released factors that can kill cholinergic neurons. This neurotoxic effect was blocked by NGF and MK-801 (a NMDA-antagonist), but not by vitamin C. Pretreatment of BCEC with intracellular pathway inhibitors did not change the neurotoxicity, but pretreatment with IL-1beta and LPS abolished the neurotoxic effect. In summary, BCEC produce and secrete molecules which induce excitotoxic cell death of cholinergic neurons. It is concluded that excitotoxic factors secreted by vascular cells may contribute to the development of cholinergic neurodegeneration as it occurs in Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Ascorbic Acid; Brain; Cell Death; Cells, Cultured; Cholinergic Fibers; Culture Media, Conditioned; Dizocilpine Maleate; Endothelial Cells; Inflammation; Interleukin-1beta; Lipopolysaccharides; Nerve Degeneration; Nerve Growth Factor; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Little is known about the effects of commonly used vitamins on serum inflammatory markers and the hormonal balance in obese postmenopausal women. We studied the effects of an 8-week open-label supplementation with vitamins C (500 mg), B6 (25 mg), B12 (1 mg), and folate (5 mg) on C-reactive protein, interleukin-6, and estradiol levels in 20 obese (body mass index > or = 30) postmenopausal women. Outcomes were assessed in a blinded fashion. Folate and vitamin B12 levels rose significantly, suggesting that the supplement was well absorbed and that participants adhered to the protocol. Weight, blood pressure, and serum lipids remained stable. C-reactive protein, interleukin-6, and leptin levels remained unchanged. Estradiol levels rose from a median of 22.0 pg/mL (IQR = 15.9-25.8) at baseline to a median of 27.8 pg/mL (IQR = 23.1-33.9) at follow-up (p = 0.003). Increments in serum estradiol caused by vitamin supplementation in postmenopausal women have not been previously described and probably merit further investigation.

Topics: Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Estradiol; Folic Acid; Inflammation; Interleukin-6; Leptin; Obesity; Postmenopause; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Ascorbic acid is present as a primary antioxidant in plasma and within cells, protecting both cytosolic and membrane components of cells from oxidative damage. The effects of intracellular ascorbic acid on F(2)-isoprostanes (biomarkers of oxidative stress) and monocyte chemoattractant protein-1 (marker of inflammatory responses) production in monocytic THP-1 cells were investigated under conditions of 2,2'-Azobis(2-methylpropionamidine)dihydrochloride (AAPH) induced oxidative stress. Cells cultured under normal conditions have extremely low ascorbate levels and the intracellular ascorbate can be augmented significantly by adding ascorbate to the culture medium. While AAPH treatment reduced cell viability, increased F(2)-isoprostanes and MCP-1 production, the presence of intracellular ascorbic acid maintained high cell viability and attenuated both F(2)-isoprostanes and MCP-1 production. Measurement of intracellular ascorbic acid and its oxidised products showed that intracellular ASC was oxidised to a significantly greater extent during AAPH treatment and may be utilised to protect the cells under conditions of oxidative stress. This study demonstrates the importance of intracellular ascorbate, which may be lacking under normal cell culture conditions, under conditions of increased oxidative stress.

Topics: Amidines; Ascorbic Acid; Cell Culture Techniques; Cell Line; Cell Membrane; Cell Survival; Chemokine CCL2; Cytosol; F2-Isoprostanes; Humans; Inflammation; Monocytes; Oxidative Stress; Time Factors

The measurement of biomarkers in blood specimens has become an integral component of many epidemiologic studies and introduces several decision points about specimen collection, processing, and storage for the investigator. We briefly discuss the current state of knowledge for four commonly assessed biomarkers: estrogens and other sex hormones, ascorbic acid and carotenoids, cytokines involved in the inflammatory response, and proteomics. Sex hormones are relatively robust to type of sample collected, delayed processing (if chilled), and long-term storage at <-70 degrees C. Ascorbic acid and carotenoids also are relatively robust to sample type and delayed processing (if chilled); however, the blood sample should not be exposed to sunlight and must be stored at <-70 degrees C to prevent substantial degradation. If ascorbic acid is of primary interest, an acid stabilizer should be added during processing. Less is known for cytokines and proteomics, although initial research suggests that these assays are sensitive to varying collection, processing, and storage methods. Overall, we recommend conducting pilot studies if any nonstandard collection, processing, or storage procedure is used. Finally, decisions about these issues depend primarily on the scientific questions of most interest, cost, flexibility, and resources.

Topics: Ascorbic Acid; Blood Preservation; Blood Specimen Collection; Carotenoids; Gonadal Steroid Hormones; Humans; Inflammation; Proteomics

In obese children, subclinical inflammation is often present and is correlated with the metabolic syndrome. Dietary factors, such as fatty acids and antioxidants, potentially modulate the association between adiposity and subclinical inflammation, but few data are available in children.. The aim of the study was to determine whether dietary fat or antioxidant intakes influence circulating tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), C-reactive protein (CRP), and leptin concentrations in overweight children.. In a cross-sectional study of 6-14-y-old normal-weight (n = 33), overweight (n = 19), and obese (n = 27) Swiss children, nutritional intakes were assessed from two 24-h dietary recalls and a 1-d dietary record. Percentage body fat from skinfold thicknesses, waist-hip ratio, and blood pressure were measured. Fasting blood samples were collected for the measurement of insulin, glucose, HDL-cholesterol, triacylglycerol, CRP, IL-6, TNF-alpha, and leptin concentrations.. CRP, IL-6, and leptin increased significantly (P < 0.02) with increasing adiposity, independent of age; TNF-alpha did not increase. Total dietary fat and the percentage of energy from fat were significant predictors of CRP concentration, independent of body mass index (P < 0.05). Meat intake was a significant predictor of IL-6 and leptin, independent of body mass index (P < 0.05). Intakes of antioxidant vitamins (vitamins E and C and beta-carotene) were significant predictors of leptin (P < 0.05) but not of CRP, IL-6, or TNF-alpha.. Overweight Swiss children as young as 6 y have elevated concentrations of inflammatory markers. Intakes of total fat and antioxidant vitamins are determinants of subclinical inflammation in this age group.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Carotenoids; Child; Cholesterol, HDL; Dietary Fats; Female; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Male; Multivariate Analysis; Overweight; Predictive Value of Tests; Skinfold Thickness; Switzerland; Triglycerides; Tumor Necrosis Factor-alpha; Vitamin E; Vitamins; Waist-Hip Ratio

Previously we reported that a mega-dose of Vitamin C enhanced the initial stage of delayed-type hypersensitivity reaction in Balb/c mice. In this study its effects were further evaluated as follows. Mice were administered Vitamin C intraperitoneally at 0.625 mg/day or at 5mg/day for variable days before, during, or after being sensitized with DNFB. T cells were isolated in each group and examined. When stimulated antigen-specifically or non-specifically in vitro, mice showed elevated thymidine uptake and a shift of cytokine secretion profiles toward Th1, i.e., elevated levels IL-2, TNF-alpha, and IFN-gamma, and lowered level of the Th2 cytokine IL-4, only when Vitamin C was administered during sensitization. T cells from those mice administered Vitamin C before sensitization or after challenge showed the same T cell properties as those from PBS-treated mice. Mice were also given 0.625 mg/day of Vitamin C during primary and/or secondary immunizations with KLH and secondary specific antibody titers in sera were measured. The total specific antibody titer was lowered in Vitamin C-treated animals whenever treatments were administered, and this was entirely attributed to decreased levels of IgG1 and IgE antibodies. Based on these results, we suggest that an exogenously administered mega-dose of Vitamin C shifts immunity in Balb/c mouse toward Th1 and that these affects occur only when Vitamin C is administered during T cell activation.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Proliferation; Cytokines; Dinitrofluorobenzene; Drug Hypersensitivity; Hemocyanins; Hypersensitivity, Delayed; Immunoglobulin E; Immunoglobulin G; Inflammation; Lymphocyte Activation; Mice; Mice, Inbred BALB C; T-Lymphocytes; Time Factors

Topics: Aged; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Biomarkers; Fibrinogen; Humans; Inflammation; Interleukin-6; Middle Aged; Thromboembolism

The major pathological ramification of Alzheimer's disease (AD) is accumulation of beta-Amyloid (Abeta) peptides in the brain. An emerging therapeutic approach for AD is elimination of excessive Ass peptides and preventing its re-accumulation. Immunization is the most effective strategy in removing preexisting cerebral Abetas and improving the cognitive capacity as shown in transgenic mice model of AD. However, active immunization is associated with adverse effect such as encephalitis with perivascular inflammation and hemorrhage. Details about the mechanistic aspects of propagation of these toxic effects are matter of intense enquiry as this knowledge is essential for the understanding of the AD pathophysiology. The present work aimed to study the oxidative vulnerability in the plasma, liver and brain of the inflammation-induced rats subjected to Ass immunization. Induction of inflammation was performed by subcutaneous injection of 0.5?ml of 2% silver nitrate. Our present result shows that the proinflammatory cytokines such as IL1alpha and TNFalpha are increased significantly in the inflammation-induced, Abeta1-42, Abeta25-35 treated groups and inflammation with Abeta25-35 treated group when compared to control, complete Freund's adjuvant and Abeta35-25 treated groups. These increased proinflammatory cytokines concurrently releases significant amount of free radicals in the astrocytes of respected groups. The present result shows that nitric oxide (NO) level was significantly higher (P<0.001) in plasma, liver and brain of the rat subjected to inflammation, Abeta1-42, Abeta25-35 and inflammation with Abeta25-35 injected groups when compared to control. The increased level of lipid peroxides (LPO) (P<0.001) and decreased antioxidant status (P<0.05) were observed in the plasma, liver and brain of inflammation-induced group when compared to control. Our result shows that significant oxidative vulnerability was observed in the inflammation with Ass treated rats when compared to other groups. Based on our results, we suggest that immunization of AD patients with Ass should be done with caution as the increase in Ass could trigger the brain inflammation in uncontrollable level.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Ascorbic Acid; Astrocytes; Brain; Catalase; Disease Models, Animal; Glutathione Peroxidase; Inflammation; Interleukin-1; Lipid Peroxidation; Liver; Nitric Oxide; Oxidation-Reduction; Peptide Fragments; Rats; Reactive Oxygen Species; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Numerous studies support the notion that an activation of sphingomyelinases and a subsequent increase of the concentration of the bioactive lipid mediator ceramide are critical in the concert of inflammatory stimuli and to the induction of apoptosis during inflammation. Here we show that patients with severe sepsis exhibit an enhanced sphingolytic activity in comparison with controls [262 pmol/(mlxh) vs. 123.6 pmol/(mlxh), P<0.005]. During the clinical course, a further increase was paralleled by the severity of illness and by fatal outcome. Moreover, we show that oxidative stress may partially account for the increased activity through posttranslational modification of the enzyme. In a murine endotoxic shock model, administration of a low molecular weight inhibitor diminished the rise in enzymatic activity and improved the survival rate. In liver specimen, inhibition of activity correlated with a reduced rate of hepato-cellular apoptosis. Our data support the concept that activation of the plasmatic isoform of sphingomyelinase may play a critical role in the development of apoptosis and organ failure in sepsis. An inhibition of the secreted isoform of sphingomyelinase should be explored further as a potential target in the complicated puzzle of sepsis.

Topics: Adult; Aged; Animals; Apoptosis; Ascorbic Acid; Blood Chemical Analysis; Ceramides; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins; Female; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Lipids; Liver; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Middle Aged; Models, Statistical; Oxidative Stress; Sepsis; Shock, Septic; Sphingomyelin Phosphodiesterase; Time Factors; Treatment Outcome

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Atrial Fibrillation; C-Reactive Protein; Electric Countershock; Humans; Inflammation; Myocarditis

Pediatric cardiac surgery with cardiopulmonary bypass (CPB) is frequently associated with neurologic deficits. We describe the postoperative EEG changes, assess their possible causes, and evaluate their relevance to neurologic outcome. Thirty-one children and five neonates with congenital heart disease were included. EEG recording started after intubation and continued until 22-96 h after CPB. In addition to conventional analysis, spectral analysis was performed for occipital and frontal electrodes, and differences between pre- and postoperative delta power (delta-deltaP) were calculated. Maximum values of occipital delta-deltaP that occurred within 48 h after CPB were correlated with clinical variables and with perioperative markers of oxidative stress and inflammation. Occipital delta-deltaP correlated with frontal delta-deltaP, and maximum delta-deltaP correlated with conventional rating. Distinct rise of deltaP was detected in 18 of 21 children without any acute or long-term neurologic deficits but only in five of 10 children with temporary or permanent neurologic deficits. Furthermore, maximally registered delta-deltaP was inversely associated with duration of CPB and postoperative ventilation. Maximal delta-deltaP was also inversely associated with the loss of plasma ascorbate (as an index of oxidative stress) and plasma levels of IL-6 and IL-8. Slow wave activity frequently occurs within 48 h after CPB. However, our data do not support the notion that EEG slowing is associated with adverse neurologic outcome. This is supported by the fact that EEG slowing was associated with less oxido-inflammatory stress.

Topics: Ascorbic Acid; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Electroencephalography; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Male; Monitoring, Physiologic; Neurons; Oxidative Stress; Postoperative Period; Time Factors

Topics: Antioxidants; Arthritis, Rheumatoid; Ascorbic Acid; Cardiovascular Diseases; Chronic Disease; Comorbidity; Diabetes Mellitus; Free Radicals; Gastritis; Inflammation; Oxidation-Reduction; Oxidative Stress; Pancreatitis

The relationship between hydrogen peroxide (H2O2) concentration in expired breath condensate (EBC) and cytology of the respiratory tract obtained from tracheal wash (TW) or bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF) antioxidant status is unknown. To examine this we analysed the concentration of H2O2 in breath condensate from healthy horses and horses affected by recurrent airway obstruction (RAO), a condition considered to be an animal model of human asthma. The degree of airway inflammation was determined by assessing TW inflammation as mucus, cell density and neutrophil scores, and by BAL cytology. ELF antioxidant status was determined by measurement of ascorbic acid, dehydroascorbate, reduced and oxidised glutathione, uric acid and alpha-tocopherol concentrations. RAO-affected horses with marked airway inflammation had significantly higher concentrations of breath condensate H2O2 than control horses and RAO-affected horses in the absence of inflammation (2.0 +/- 0.5 micromol/l. 0.4 +/- 0.2 micromol/l and 0.9 +/- 0.2 micromol/l H2O2, respectively; p < 0.0001). The concentration of breath condensate H2O2 was related inversely to the concentration of ascorbic acid in ELF (r = -0.80; p < 0.0001) and correlated positively with TW inflammation score (r = 0.76, p < 0.0001) and BAL neutrophil count (r = 0.80, p < 0.0001). We conclude that the concentration of H2O2 in breath condensate influences the ELF ascorbic acid concentration and provides a non-invasive diagnostic indicator of the severity of neutrophilic airway inflammation.

Topics: Airway Obstruction; Animals; Ascorbic Acid; Breath Tests; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cell Count; Dehydroascorbic Acid; Diagnosis, Differential; Disease Models, Animal; Glutathione; Horses; Hydrogen Peroxide; Inflammation; Mucus; Neutrophils; Respiratory Mucosa; Respiratory System; Spectrophotometry

Experimental hypercholesterolemia (HC) may lead to microvascular neovascularization, but the underlying pathogenic mechanism remains unclear. We tested the hypothesis that HC-induced intra-renal neovascularization is associated with inflammation and increased oxidative stress, and would be prevented by chronic antioxidant intervention. Kidneys were excised from pigs after a 12-wk normal (n = 10) or HC diet (n = 8), or HC diet supplemented daily with antioxidant vitamins C (1 g) and E (100 IU/kg) (HC + vitamins, n = 7). Renal cortical samples were then scanned three dimensionally with micro-computed tomography, and microvessels were counted in situ. Blood and tissue samples were removed for measurements of superoxide dismutase (SOD) activity, protein expression of the NADP(H)-oxidase subunits gp91phox, p47phox, and p67phox, vascular endothelial growth factor (VEGF) levels and mRNA, VEGF receptors (Flt-1 and Flk-1), the proinflammatory transcription factor NFkappaB, and the oxidized LDL receptor LOX-1. Microvascular spatial density was significantly elevated in HC compared with normal kidneys but preserved in HC + vitamins. Expression of gp91phox and p67phox was decreased in HC pigs after antioxidant intervention, and SOD improved. The increased renal expression of VEGF and Flk-1 in HC was blunted in HC + vitamins, as were the significant increases in LOX-1, NFkappaB, and interstitial fibrosis. This study shows that renal cortical neovascularization elicited by diet-induced HC is associated with renal inflammation, fibrosis, and upregulation of VEGF and its receptor Flk-1, likely mediated by increased endogenous oxidative stress. Chronic antioxidant supplementation may preserve the kidney in HC.

Topics: Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Body Weight; DNA, Complementary; Enzyme-Linked Immunosorbent Assay; Female; Fibrosis; Hypercholesterolemia; Image Processing, Computer-Assisted; Inflammation; Kidney; Membrane Glycoproteins; Microcirculation; NADPH Oxidase 2; NADPH Oxidases; Neovascularization, Pathologic; NF-kappa B; Oxidation-Reduction; Phosphoproteins; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Superoxide Dismutase; Swine; Tomography, X-Ray Computed; Vascular Endothelial Growth Factor A

There is evidence for a role of oxidant stress and inflammation in atrial fibrillation (AF). Statins have both antioxidant and antiinflammatory properties. We compared the effects of simvastatin with those of antioxidant vitamins on AF promotion by atrial tachycardia in dogs.. We studied dogs subjected to atrial tachypacing (ATP) at 400 bpm in the absence and presence of treatment with simvastatin, vitamin C, and combined vitamins C and E. Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. Atrioventricular block was performed to control ventricular rate. Mean duration of induced AF was increased from 42+/-18 to 1079+/-341 seconds at terminal open-chest study after tachypacing alone (P<0.01), and atrial effective refractory period (ERP) at a cycle length of 300 ms was decreased from 117+/-5 to 76+/-6 ms (P<0.01). Tachypacing-induced ERP shortening and AF promotion were unaffected by vitamin C or vitamins C and E; however, simvastatin suppressed tachypacing-induced remodeling effects significantly, with AF duration and ERP averaging 41+/-15 seconds and 103+/-4 ms, respectively, after tachypacing with simvastatin therapy. Tachypacing downregulated L-type Ca2+-channel alpha-subunit expression (Western blot), an effect that was unaltered by antioxidant vitamins but greatly attenuated by simvastatin.. Simvastatin attenuates AF promotion by atrial tachycardia in dogs, an effect not shared by antioxidant vitamins, and constitutes a potentially interesting new pharmacological approach to preventing the consequences of atrial tachycardia remodeling.

Topics: Animals; Antioxidants; Ascorbic Acid; Atrial Fibrillation; Calcium Channels, L-Type; Cardiac Pacing, Artificial; Dogs; Drug Evaluation, Preclinical; Drug Therapy, Combination; Gene Expression Regulation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Oxidative Stress; Refractory Period, Electrophysiological; Simvastatin; Vitamin E

Current evidence supports a significant association between fruit and vegetable intake and health. In this study, we assessed the effect of consuming a vegetable-soup "gazpacho" on vitamin C and biomarkers of oxidative stress and inflammation in a healthy human population. We also examined the association between vitamin C and F(2)-isoprostanes (8-epiPGF(2alpha)), uric acid (UA), prostaglandin E(2) (PGE(2)), monocyte chemotactic protein-1 (MCP-1), and the cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. Gazpacho is a Mediterranean dish defined as a ready-to-use vegetable soup, containing approximately 80% crude vegetables rich in vitamin C. Subjects (6 men, 6 women) enrolled in this study consumed 500 mL/d of gazpacho corresponding to an intake of 72 mg of vitamin C. On d 1, subjects consumed the gazpacho in one dose; from d 2 until the end of the study, d 14, 250 mL was consumed in the morning and 250 mL in the afternoon. Blood was collected before drinking the soup (baseline) and on d 7 and 14. Baseline plasma vitamin C concentrations did not differ between men and women (P = 0.060). Compared with baseline, the vitamin C concentration was significantly higher on d 7 and 14 of the intervention in both men and women (P < 0.05). Baseline plasma levels of UA and F(2)-isoprostanes were higher (P < or = 0.002) in men than in women. The F(2)-isoprostanes decreased on d 14 in men and women (P < or = 0.041), and UA decreased in men (P = 0.028). The concentrations of vitamin C and 8-epiPGF(2alpha) were inversely correlated (r = -0.585, P = 0.0002). Plasma PGE(2) and MCP-1 concentrations decreased in men and women (P < or = 0.05) on d 14, but those of TNF-alpha, IL-1beta, and IL-6 did not change. Consumption of the vegetable soup decreases oxidative stress and biomarkers of inflammation, which indicates that the protective effect of vegetables may extend beyond their antioxidant capacity.

Topics: Adult; Ascorbic Acid; Biomarkers; Chemokine CCL2; Diet; Diet, Mediterranean; Dinoprost; Dinoprostone; Female; Food Handling; Humans; Inflammation; Interleukin-1; Interleukin-6; Male; Oxidative Stress; Solutions; Tumor Necrosis Factor-alpha; Uric Acid; Vegetables

alpha,beta-Unsaturated aldehydes such as 4-hydroxy-2-nonenal (HNE) and other electrophilic lipid peroxidation (LPO) products may contribute to the pathogenesis of cancer, cardiovascular diseases, and other age-related diseases by cytotoxic, genotoxic, and proinflammatory mechanisms. The notion that vitamin C (ascorbic acid) acts as a biological antioxidant has been challenged recently by an in vitro study showing that ascorbic acid promotes, rather than inhibits, the formation of genotoxic LPO products from the lipid hydroperoxide, hydroperoxy octadecadienoic acid [Lee, S. H., Oe, T. & Blair, I. A. (2001) Science 292, 2083-2086]. Here, we demonstrate that ascorbic acid acts as a nucleophile and forms Michael-type conjugates with electrophilic LPO products. Several ascorbyl-LPO product conjugates, resulting from the interaction of ascorbic acid with hydroperoxy octadecadienoic acid in vitro, were identified by tandem MS, including ascorbyl conjugates of HNE, 4-oxo-2-nonenal, and presumably, 12-oxo-9-hydroxy-10-dodecenoic acid. The same ascorbyl-LPO product conjugates were detected in human plasma. The concentration of the ascorbyl-HNE conjugate in plasma from 11 healthy subjects was found to be 1.30 +/- 0.74 microM (mean +/- SD). Our data identify ascorbylation (vitamin C conjugation) as a previously unrecognized, biologically relevant pathway for the elimination of electrophilic LPO products, and have implications for the prevention and treatment of chronic inflammatory diseases, as well as the development of novel biomarkers of oxidative stress.

Topics: Aldehydes; Ascorbic Acid; Calibration; Chromatography, Liquid; Electrons; Fatty Acids, Monounsaturated; Glutathione; Humans; Inflammation; Linoleic Acids; Lipid Metabolism; Lipid Peroxidation; Lipoxygenase Inhibitors; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Chemical; Mutagens; Oxidative Stress; Plasma; Protein Conformation; Protein Structure, Tertiary; Spectrometry, Mass, Electrospray Ionization; Time Factors

To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined endogenous antioxidant reactivity and inflammatory response in Caco-2 cell line. When differentiated Caco-2 cells were incubated with iron/ascorbate for 1-24 h, they exhibited increased malondialdehyde levels and decreased polyunsaturated fatty acid proportion in favor of saturated fatty acids. These modifications were accompanied with alterations in membrane fluidity and permeability. The oxidative stress did not induce changes in the antioxidant enzyme activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase, or in cellular glutathione content. However, iron/ascorbate-mediated lipid peroxidation promoted inhibitor-kappaB degradation and NF-kappaB activation, as well as gave rise to IL-8, cyclooxygenase-2, and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.

Topics: Ascorbic Acid; Caco-2 Cells; Cyclooxygenase 2; Electric Impedance; Fatty Acids; Free Radical Scavengers; Humans; I-kappa B Proteins; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Intestinal Mucosa; Iron; Isoenzymes; Lipid Peroxidation; Malondialdehyde; Membrane Fluidity; Membrane Proteins; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidoreductases; Permeability; Prostaglandin-Endoperoxide Synthases

Renal artery stenosis (RAS) may lead to renal injury, partly mediated through increased oxidative stress. However, the potential effects of chronic oral antioxidant intervention on the stenotic kidney remain unknown. This study was designed to test the hypothesis that chronic antioxidant vitamin supplementation in RAS would preserve renal function and structure. Single-kidney hemodynamics and function were quantified in vivo in pigs using electron-beam CT after 12 weeks of unilateral RAS (n=7), a similar degree of RAS orally supplemented with vitamins C (1 g) and E (100 IU/kg) (RAS+Vitamins, n=7), or controls (normal, n=7). Renal tissue was studied ex vivo using Western blotting and immunohistochemistry. Mean arterial pressure was similarly elevated in both RAS groups, while ischemic renal volume and glomerular filtration rate were similarly reduced. Renal blood flow was decreased in RAS compared with normal (326.5+/-99.9 versus 553.4+/-48.7 mL/min, respectively, P=0.01), but preserved in RAS+Vitamins (485.2+/-104.1 mL/min, P=0.3 versus normal). The marked increase in the expression of the NADPH-oxidase subunits p47phox and p67phox, nitrotyrosine, endothelial and inducible nitric oxide synthase, and nuclear factor-kappaB observed in RAS (P<0.05 versus normal) was normalized in RAS+Vitamins (P>0.1). Furthermore, trichrome staining and the expression of transforming growth factor-beta and tissue inhibitor of matrix-metalloproteinase-1 were also decreased in RAS+Vitamins. In conclusion, chronic blockade of the oxidative stress pathway in RAS using antioxidant vitamins improved renal hemodynamics and decreased oxidative stress, inflammation, and fibrosis in the ischemic kidney. These observations underscore the involvement of oxidative stress in renal injury in RAS and support a role for antioxidant vitamins in preserving the ischemic kidney.

Topics: Animals; Antioxidants; Ascorbic Acid; Fibrosis; Hemodynamics; Inflammation; Kidney; Oxidation-Reduction; Oxidative Stress; Regional Blood Flow; Renal Artery Obstruction; Swine; Vitamin E

We sought to determine the role of oxidative stress in the development of vascular dysfunction in inflammation.. Hyporeactivity to catecholamines and other vasoconstrictors is present in acute inflammation. Because oxidative stress plays a significant role in inflammation, impaired responsiveness may be overcome by anti-oxidants.. In randomized, double-blind, cross-over studies, forearm blood flow (FBF) responses to norepinephrine (NE), angiotensin II (ANG II), and vasopressin (VP) were assessed before and 4 h after induction of systemic inflammation by low doses of Escherichia coli endotoxin (lipopolysaccharide [LPS], 20 IU/kg intravenously) or after placebo in healthy volunteers. Furthermore, the effect of intra-arterial vitamin C (24 mg/min) or placebo on NE-induced or ANG II-induced vasoconstriction was studied after LPS.. Administration of LPS caused systemic and forearm vasodilation, increased white blood cell count, elevated body temperature, and reduced vitamin C plasma concentrations. Lipopolysaccharide decreased the responses of FBF to NE by 59%, to ANG II by 25%, and to VP by 51% (n = 9, p < 0.05, all effects). Co-administration of vitamin C completely restored the response to NE and to ANG II, which was comparable to that observed under baseline conditions (n = 8).. E. coli-endotoxemia reduces FBF responsiveness to vasoconstrictors. The hyporeactivity can be corrected by high doses of vitamin C, suggesting that oxidative stress may represent an important target for inflammation-induced impaired vascular function.

Topics: Adult; Angiotensin II; Antioxidants; Ascorbic Acid; Endotoxemia; Escherichia coli Infections; Humans; Inflammation; Male; Oxidative Stress; Regional Blood Flow; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Gamma-tocopherol (gammaT) complements alpha-tocopherol (alphaT) by trapping reactive nitrogen oxides to form a stable adduct, 5-nitro-gammaT [Christen et al., PNAS 94:3217-3222; 1997]. This observation led to the current investigation in which we studied the effects of gammaT supplementation on plasma and tissue vitamin C, vitamin E, and protein nitration before and after zymosan-induced acute peritonitis. Male Fischer 344 rats were fed for 4 weeks with either a normal chow diet with basal 32 mg alphaT/kg, or the same diet supplemented with approximately 90 mg d-gammaT/kg. Supplementation resulted in significantly higher levels of gammaT in plasma, liver, and kidney of control animals without affecting alphaT, total alphaT+gammaT or vitamin C. Intraperitoneal injection of zymosan caused a marked increase in 3-nitrotyrosine and a profound decline in vitamin C in all tissues examined. Supplementation with gammaT significantly inhibited protein nitration and ascorbate oxidation in the kidney, as indicated by the 29% and 56% reduction of kidney 3-nitrotyrosine and dehydroascorbate, respectively. Supplementation significantly attenuated inflammation-induced loss of vitamin C in the plasma (38%) and kidney (20%). Zymosan-treated animals had significantly higher plasma and tissue gammaT than nontreated pair-fed controls, and the elevation of gammaT was strongly accentuated by the supplementation. In contrast, alphaT did not significantly change in response to zymosan treatment. In untreated control animals, gammaT supplementation lowered basal levels of 3-nitrotyrosine in the kidney and buffered the starvation-induced changes in vitamin C in all tissues examined. Our study provides the first in vivo evidence that in rats with high basal amounts of alphaT, a moderate gammaT supplementation attenuates inflammation-mediated damage, and spares vitamin C during starvation-induced stress without affecting alphaT.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; gamma-Tocopherol; Inflammation; Kidney; Male; Nitrogen; Oxygen; Proteins; Rats; Rats, Inbred F344; Tissue Distribution; Tyrosine; Vitamin E; Zymosan

Study of relationship between the content of lipid peroxidation (LPO) products in the blood of patients with benign prostatic hyperplasia (BPH) and resistance to infectious inflammatory complications (IIC) of transurethral electroresection of the prostate showed that decreased content of circulating lipoperoxides promoted the development of postoperative IIC. Before the operation blood levels of LPO products were increased in BPH patients who did not develop IIC postoperation in comparison with normal controls. Three intravenous injections of ascorbic acid in a single dose of 1000 mg after transurethral electroresection of the prostate led to an increase in the blood level of LPO products and promoted a decrease in the incidence of postoperative IIC.

Topics: Antioxidants; Ascorbic Acid; Bacterial Infections; Biomarkers; Humans; Inflammation; Injections, Intravenous; Lipid Peroxidation; Male; Postoperative Complications; Prostatic Hyperplasia; Transurethral Resection of Prostate

Reperfusion injury is considered primarily an inflammatory response to oxidative stress. In vitro, oxygen free radicals induce the formation of oxidized phospholipids with platelet-activating factor (PAF) activity (PAF-like lipids). We examined the following: 1) whether PAF and PAF-like lipids are released during reperfusion; 2) the relationship between these phospholipids and oxidative damage on the one hand, and leukocyte recruitment in renal tissue on the other; and 3) whether antioxidant treatment influences the behavior of these phospholipids, the renal inflammatory response, and the outcome of postischemic acute renal failure. After 60 min of warm renal ischemia in rabbits, a release of PAF and, particularly, PAF-like lipids was seen in the first 15 min of reperfusion. In addition, the release of those phospholipids was associated with intense tissue DNA oxidation and with an increase in myeloperoxidase activity. Vitamin C was able to attenuate these postischemic oxidative changes, decrease PAF and PAF-like lipid levels, and, consequently, reduce myeloperoxidase activity. After 40 min of warm renal ischemia in rats, vitamin C treatment ameliorated renal function and structure. This is the first in vivo demonstration of the release of phospholipid oxidation products as part of an oxidative-inflammatory response after renal ischemia-reperfusion, with the release of phospholipid oxidation products significantly reduced by antioxidant treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Ascorbic Acid; Creatinine; Deoxyguanosine; DNA Damage; Inflammation; Ischemia; Kidney; Lipoproteins, LDL; Oxidative Stress; Platelet Activating Factor; Rabbits; Rats

The tissue-fixed macrophage (Mphi) is a key cell in the coordination of the excessive systemic immunoinflammatory response underlying the adult respiratory distress syndrome (ARDS). Macrophage-generated reactive oxygen intermediates (ROIs) are involved in both tissue destruction via lipid peroxidation and in the activation of these inflammatory cells. It is unclear whether oxidant-induced activation involves an extracellular effect and membrane destabilization or occurs through intracellular alteration of the redox state and direct involvement as second messengers. In this study, we compare the differential effects of known intracellular vs. extracellular antioxidants on the Mphi response to endotoxin. Rabbit alveolar Mphi were obtained by bronchoalveolar lavage and exposed to either the extracellular antioxidants [vitamin C (VC) (10-1000 microM), Trolox (100-1000 microM, superoxide dismutase (SOD) (10-500 microM))] or the intracellular antioxidants [N-acetylcysteine (NAC) (0.1-10 mM) or butylated hydroxyanisole (BHA) (10-200 microM)] for 1 h. Cells were subsequently stimulated with lipopolysaccharide at 10 ng/mL. After 18 h, supernatants were analyzed for tumor necrosis factor (TNF) and F2 isoprostane (F2ISP) production and cellular monolayers for procoagulant activity (PCA). A dose response inhibition of both TNF and PCA production was demonstrated after both NAC and BHA pretreatment but not with VC, Trolox, or SOD. In addition, northern blots revealed inhibition of TNF mRNA production by both NAC and BHA. F2ISP, a marker of membrane lipid peroxidation, was inhibited by BHA and Trolox but not NAC, VC, or SOD. In conclusion, antioxidants that are incorporated intracellularly are expected to be beneficial in the treatment of excessive inflammatory responses through the interruption of redox dependent signal transduction pathways and subsequent modulation of the Mphi proinflammatory response.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Blood Coagulation Factors; Butylated Hydroxyanisole; Cells, Cultured; Chromans; Endotoxins; F2-Isoprostanes; Inflammation; Macrophages, Alveolar; Male; Rabbits; Reactive Oxygen Species; Respiratory Distress Syndrome; Signal Transduction; Superoxide Dismutase; Tumor Necrosis Factor-alpha

This study examined the effects of antioxidant vitamins A, C, and E on nuclear transcription factor-kappa B (NF-kappaB) nuclear translocation, on secretion of inflammatory cytokines by cardiac myocytes, and on cardiac function after major burn trauma.. Adult rats were divided into four experimental groups: group I, shams; group II, shams given oral antioxidant vitamins (vitamin C, 38 mg/kg; vitamin E, 27 U/kg; vitamin A, 41 U/kg 24 hours before and immediately after burn); group III, burns (third-degree scald burn over 40% total body surface area) given lactated Ringer's solution (4 mL/kg/% burn); and group IV, burns given lactated Ringer's solution plus vitamins as described above. Hearts were collected 4, 8, 12, and 24 hours after burn to assay for NF-kappaB nuclear translocation, and hearts collected 24 hours after burn were examined for cardiac contractile function or tumor necrosis factor-alpha secretion by cardiomyocytes.. Compared with shams, left ventricular pressure was lower in burns given lactated Ringer's solution (group III) (88 +/- 3 vs. 64 +/- 5 mm Hg, p < 0.01) as was +dP/dt max (2,190 +/- 30 vs. 1,321 +/- 122 mm Hg/s) and -dP/dt max (1,775 +/- 71 vs. 999 +/- 96 mm Hg, p < 0.01). Burn injury in the absence of vitamin therapy (group III) produced cardiac NF-kappaB nuclear migration 4 hours after burn and cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by 24 hours after burn. Antioxidant therapy in burns (group IV) improved cardiac function, producing left ventricular pressure and +/-dP/dt (82 +/- 2 mm Hg, 1,880 +/- 44 mm Hg, and 1,570 +/- 46 mm Hg/s) comparable to those measured in shams. Antioxidant vitamins in burns inhibited NF-kappaB nuclear migration at all times after burn and reduced burn-mediated cytokine secretion by cardiomyocytes.. These data suggest that antioxidant vitamin therapy in burn trauma provides cardioprotection, at least in part, by inhibiting translocation of the transcription factor NF-kappaB and interrupting cardiac inflammatory cytokine secretion.

Topics: Animals; Antioxidants; Ascorbic Acid; Body Surface Area; Burns; Disease Models, Animal; Drug Evaluation, Preclinical; Hemodynamics; Inflammation; Injury Severity Score; Interleukin-1; Interleukin-6; Myocardial Contraction; Myocardium; NF-kappa B; Oxidative Stress; Protein Transport; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin E

Peripheral arterial disease (PAD) is a severe atherosclerotic condition frequently accompanied by inflammation and oxidative stress. We hypothesized that vitamin C antioxidant levels might be low in PAD and are related to inflammation and disease severity.. We investigated vitamin C (L-ascorbic acid) levels in 85 PAD patients, 106 hypertensives without PAD, and 113 healthy subjects. Serum L-ascorbic acid concentrations were low among PAD patients (median, 27.8 micromol/L) despite comparable smoking status and dietary intake with the other groups (P<0.0001). Subclinical vitamin C deficiency (<11.4 micromol/L), confirmed by low serum alkaline phosphatase activity, was found in 14% of the PAD patients but not in the other groups. Serum C-reactive protein (CRP) concentrations were significantly higher in PAD patients (P<0.0001) and negatively correlated with L-ascorbic acid levels (r=-0.742, P<0.0001). In stepwise multivariate analysis, low L-ascorbic acid concentration in PAD patients was associated with high CRP level (P=0.0001), smoking (P=0.0009), and shorter absolute claudication distance on a standardized graded treadmill test (P=0.029).. Vitamin C concentrations are lower in intermittent claudicant patients in association with higher CRP levels and severity of PAD. Future studies attempting to relate vitamin C levels to disease occurrence should include in their analysis an inflammatory marker such as CRP.

Topics: Aged; Arteriosclerosis; Ascorbic Acid; Aspirin; C-Reactive Protein; Female; Fibrinogen; Humans; Hypertension; Inflammation; Lipids; Male; Middle Aged; Multivariate Analysis; Peripheral Vascular Diseases; Severity of Illness Index; Smoking

Iron supplementation may increase disease activity in ulcerative colitis, possibly through the production of reactive oxygen species from the Fenton reaction.. To assess the effects of two doses of oral iron on intestinal inflammation and oxidative stress in experimental colitis.. Colitis was induced in rats by giving 5% dextran sulphate sodium in drinking water for 7 days. First, using a 2 x 2 factorial design, rats with or without dextran sulphate sodium received the regular diet or a diet containing iron 3%/kg diet. Second, rats with dextran sulphate sodium-induced colitis were supplemented with iron 0.3%/kg diet and compared with rats on dextran sulphate sodium and regular diet. The body weight change, histological scores, colon length, rectal bleeding, plasma and colonic lipid peroxides, colonic glutathione peroxidase and plasma vitamin E and C were measured. Faecal analysis for haem and total, free and ethylenediaminetetra-acetic acid-chelatable iron was also performed.. Iron 3% and iron 0.3% increased the activity of dextran sulphate sodium-induced colitis, as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. This was associated with increased lipid peroxidation and decreased antioxidant vitamins. Faecal iron available to the Fenton reaction was increased in a dose-dependent manner.. Iron supplementation taken orally enhanced the activity of dextran sulphate sodium-induced colitis and is associated with an increase in oxidative stress.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Colitis; Dextran Sulfate; Dietary Supplements; Disease Models, Animal; Drug Interactions; Glutathione Peroxidase; In Vitro Techniques; Inflammation; Intestines; Iron; Lipid Peroxidation; Male; Mucous Membrane; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Vitamin E

We examined the effects of ozone (O(3)) and endogenous antioxidant transport on canine peripheral airway function, central airway function, epithelial integrity, and inflammation. Dogs were either untreated or pretreated with probenecid (an anion-transport inhibitor) and exposed for 6 h to 0.2 parts/million O(3). Peripheral airway resistance (Rpa) and reactivity (DeltaRpa) were monitored in three sublobar locations before and after exposure to either air or O(3). Pulmonary resistance and transepithelial potential difference in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid (BALF) was collected before, during, and after exposure. O(3) increased Rpa and DeltaRpa only in probenecid-treated dogs and in a location-dependent fashion. Pulmonary resistance and potential difference in bronchus increased after O(3) exposure regardless of treatment. O(3) markedly increased BALF neutrophils only in untreated dogs. With the exception of hexanal, O(3) did not alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BALF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 parts/million O(3) represents a subthreshold stimulus in relation to its effects on peripheral airway function in dogs, 2) antioxidant transport contributes to the maintenance of normal airway tone and reactivity under conditions of oxidant stress, 3) O(3)-induced changes in Rpa and DeltaRpa are dependent on location, and 4) peripheral airway hyperreactivity and inflammation reflect independent responses to O(3) exposure. Finally, although anion transport mitigates the effect of O(3) on peripheral airway function, it contributes to the development of airway inflammation and may represent a possible target for anti-inflammatory prevention or therapy.

Topics: Airway Resistance; Aldehydes; Animals; Antioxidants; Ascorbic Acid; Biological Transport, Active; Bronchoalveolar Lavage Fluid; Cell Count; Chromans; Dogs; Inflammation; Male; Oxidants, Photochemical; Ozone; Peroxides; Probenecid; Proteins; Respiratory System; Uricosuric Agents

Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L, all indexes of inflammation were relatively high, whereas those with concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

Topics: Adolescent; Adult; Ascorbic Acid; beta Carotene; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; Cytokines; Dose-Response Relationship, Drug; Female; Humans; Infant; Inflammation; Interleukin-6; Leukocyte Elastase; Lipid Peroxidation; Lung Diseases; Male; Malondialdehyde; Nutritional Status; Orosomucoid; Seasons; Tumor Necrosis Factor-alpha; Vitamin E

Reactive oxygen species (ROS) have been implicated in a variety of pathological processes. The generation of highly reactive oxygen metabolites is an integral feature of normal cellular metabolism (mitochondrial respiratory chain, phagocytosis, arachidonic acid metabolism, ovulation and fertilization), however their production can multiply during pathological circumstances. Free oxygen radicals act either on the extracellular matrix or directly upon cellular membranes themselves. The fundamental defense of the organism against ROS include scavenger enzymes (superoxide dismutase, catalase, glutathione peroxidase) and lipid- and water soluble antioxidant compound (ascorbic acid, glutathione, albumin, transferrin, etc.). Their role in ischemia-reperfusion models have now been comprehensively investigated and it has become clear that ROS is to be blamed for the bulk of post-ischemic injuries, hence the basis for newly established antioxidant therapy in such cases. Also more and more studies have concluded a pivotal role of ROS in degenerative and inflammatory conditions, post-radiation processes and aging. Therefore it seems as we are continuously shedding light on the crucial part played by these molecules regarding a wide range of pathologies, we are discovering new therapeutic windows that would clinically assist us in managing such conditions.

Topics: Aging; Albumins; Antioxidants; Arachidonic Acids; Ascorbic Acid; Catalase; Cell Membrane; Cell Respiration; Extracellular Matrix; Female; Fertilization; Free Radical Scavengers; Free Radicals; Glutathione; Glutathione Peroxidase; Humans; Inflammation; Ischemia; Mitochondria; Ovulation; Phagocytosis; Radiation Injuries; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase; Transferrin

In the rabbit, an acute inflammatory reaction triggered by the subcutaneous administration of turpentine induces in hepatic tissues an oxidative stress, as well as a decrease in activity of enzymatic scavengers of reactive oxygen species (ROS). The objective of this study was to investigate, the repercussions of a local inflammatory reaction on the antioxidant capacity and markers of systemic oxidative stress in plasma. To this purpose, rabbits received a.s.c. injection of turpentine (5 mL/kg) or NaCl 0.9% (w/v). Blood samples were collected at different times during the 48 hours of the experiment to evaluate: firstly, the antilipoperoxidant activity of plasma by measuring the inhibition of autoxidation of brain homogenate, and the concentrations of tocopherol and ascorbic acid; secondly, the severity of oxidative stress in plasma by assaying the concentration of thiobarbituric acid reactive substances (TBARS), and the concentration of ascorbyl radical. The results show that the antilipoperoxidant capacity of plasma gradually increased to be 167% higher than baseline values (p < 0.05) after 48 hours of experiment. alpha-Tocopherol and ascorbic acid levels increased by 49% and 80%, respectively (p < 0.05) during the first 24 hours. Lipid peroxidation continuously increased to be 98% higher than baseline values (p < 0.05) at 48 hours, while ascorbyl radical levels were not modified (p < 0.05). In summary, an acute local inflammatory reaction causes a steady progression of oxidative stress, while it stimulates the antilipoperoxidant activity of plasma, to which alpha-tocopherol and ascorbic acid appear to contribute, essentially early in the inflammation.

Topics: Animals; Ascorbic Acid; Inflammation; Injections, Subcutaneous; Lipid Peroxidation; Male; Oxidative Stress; Rabbits; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Turpentine; Vitamin E

We determined whether plasma levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) accurately reflect the tissue GSH and GSSG levels in lung and liver during a progressive acute inflammation-induced increased oxidant activity. We also determined whether plasma GSH also reflected other antioxidant defenses. Male Wistar rats (n = 38) were given intraperitoneal zymosan (.75 mg/g body weight) producing an acute progressive peritonitis and generalized inflammation. Animals were resuscitated then killed at 4 or 24 h. Plasma and tissue levels of GSH, GSSG, vitamin C, alpha-tocopherol, and catalase were measured. Conjugated dienes and malondialdehyde were used as tissue markers of lipid peroxidation. We found lung and liver tissue GSH to be decreased significantly at 4 h while GSSG was increased. Lipid peroxidation was also present in the lung. At 24 h, GSH remained decreased in liver and GSSG remained increased in lung along with the lipid peroxides conjugated dienes and malondialdehyde. In addition, overall antioxidant defenses were decreased in both lung and liver. Plasma GSH remained decreased at 24 h corresponding with the decrease in liver GSH as well as the decrease in other plasma and tissue antioxidants. However, plasma GSSG levels were not significantly increased, at any time point, indicating plasma GSSG does not accurately reflect tissue oxidant activity.

Topics: Acute Disease; Animals; Antioxidants; Ascorbic Acid; Catalase; Glutathione; Glutathione Disulfide; Inflammation; Lipid Peroxidation; Liver; Lung; Male; Rats; Rats, Wistar; Vitamin E; Zymosan

Acute zymosan-induced peritonitis in rats produces lung inflammation and lipid peroxidation. The effect of this process on plasma and lung tissue ascorbic acid was determined, as was the effect of infusing 150 mg/kg of ascorbic acid immediately after zymosan on the degree of lung insult. Ascorbic acid levels were significantly decreased in plasma and lung tissue at 24 h after zymosan, and lung tissue conjugated diene and neutrophil content was also significantly increased. Vitamin C infusion increased postzymosan plasma levels by 50% over normal control levels. However, lung tissue ascorbic acid was still decreased, and no decrease in the lung injury process was noted. Added ascorbic acid also did not prevent a decrease in plasma vitamin E with the peritonitis. We conclude that the amount of ascorbic acid given in this study did not diminish the lung oxidant inflammatory changes. An insufficient dose or inadequate time for plasma ascorbic acid to equilibrate with the lung cytosol are possible explanations for the lack of attenuation of lung oxidant stress.

Topics: Acute Disease; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Inflammation; Lipid Peroxidation; Lung; Male; Oxidation-Reduction; Peritonitis; Pulmonary Edema; Rats; Rats, Wistar; Vitamin E; Vitamin E Deficiency; Zymosan

The aim of this study was to explore whether intraperitoneal administration of ascorbic acid (AA) at a dose of 500 mg/kg, once a day for 3 following days, affected the peroxidase (PO) activity in inflamed feet of mice. The foot inflammatory reaction induced by the carrageenan (CAR), n-formyl-methionyl-leucyl-phenylalanine (FMLP) and xanthine-xanthine oxidase was accompanied by suppression of PO activity. Administration of AA, having no effect on the degree of foot oedema, skin temperature and microscopic picture of tissue specimens significantly enhanced the decline in PO activity provoked by inflammatory agents. This activity decreased 2.0-, 1.6- and 1.9-fold (p < 0.001, p < 0.01, p < 0.05) when inflammatory response was induced with FMLP, CAR and X-XO, respectively. Also in vitro AA (50-100 micrograms/ml) inhibited PO activity of leukocyte lysate and foot extract obtained from untreated animals. In conclusion we found that AA, having no effect on inflammatory response, significantly enhanced inhibition of PO activity in inflamed tissues in mice which could be a result of direct action of AA on the enzyme molecule.

Topics: Animals; Ascorbic Acid; Carrageenan; Edema; Foot; Inflammation; Male; Mice; Mice, Inbred BALB C; N-Formylmethionine Leucyl-Phenylalanine; Peroxidase; Skin Temperature; Xanthine; Xanthine Oxidase; Xanthines

Fructus Corni (FC) decoction inhibits the increase of peritoneal capillary permeability by ip 0.7% acetic acid in mice, the proliferation of granuloma formed by implanting cotton pellets in rats, the swelling of mouse pinnea with xylene and the edema of hind paw induced by injection of fresh egg white 0.1 ml in rats. FC decreases the contents of ascorbic acid in adrenal, but has no marked effect on the contents of prostaglandin E in inflammatory tissue of rats. These results indicate that the inhibitory effect of FC on the inflammatory process may be related to pituitary-adrenal axis.

Topics: Adrenal Glands; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Capillary Permeability; Drugs, Chinese Herbal; Granuloma, Foreign-Body; Inflammation; Male; Mice; Prostaglandins E; Rats; Rats, Inbred Strains

We studied prospectively the effects of 2% hydroxypropylmethylcellulose (HPMC), instilled in to the anterior chamber during extracapsular cataract extraction with posterior chamber intraocular lens implantation in 122 patients. Significant pressure rise was noted at 12 and 24 hours post-operatively when HPMC was not removed at the end of surgery. This was prevented by washing HPMC from the anterior chamber at the end of surgery, or by using either acetazolamide or a combination of oxyphenbutazone and vitamin C without washing HPMC. There was no difference in intraocular inflammation between controls and the HPMC groups. The group receiving combined oxyphenbutazone and vitamin C had the least, the differences between these two groups being sufficient.

Topics: Acetazolamide; Anterior Chamber; Ascorbic Acid; Cataract Extraction; Female; Humans; Hypromellose Derivatives; Inflammation; Intraocular Pressure; Lenses, Intraocular; Male; Methylcellulose; Ophthalmic Solutions; Oxyphenbutazone; Postoperative Complications; Prospective Studies; Time Factors

Ascorbic acid as a scavenger of oxidants derived from human polymorphonuclear leukocytes (PMNL) may have clinical significance in antioxidant prevention of emphysema. However, there is a risk relevant to its administration because this drug was reported to enhance PMNL chemotactic response and thus could create protease burden in the lower airways. In this study we have investigated the effect of ascorbic acid on the PMNL influx to the place of inflammation developed in the mouse pleural cavity after injection of zymosan-activated serum (ZAS). We also evaluated the influence of ascorbic acid on human PMNL spontaneous migration, chemotaxis to ZAS and n-formyl-methionyl-leucyl-phenylalanine (FMLP) under agarose. The previous ascorbic acid intraperitoneal administration (single dose 10 mg per day for 3 following days) inhibited leukocyte influx. Total number of cells found in the cavity, number of PMNL and lymphocytes was 2.4, 3.5, 1.7-fold lower than in animals without ascorbic acid, respectively. In vitro ascorbic acid (concentrations of 1 to 10 mg/dl) enhanced PMNL spontaneous migration, concentrations 10 mg/dl and higher inhibited PMNL chemotaxis to ZAS and had no influence on migration of the cells toward FMLP. These results suggest that ascorbic acid may be useful for prevention of lung oxidant injury not only as oxidant scavenger but also as an inhibitor of PMNL influx to the pulmonary tissue.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Migration Inhibition; Inflammation; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Neutrophils; Phagocytes

Topics: Ascorbic Acid; Cells, Cultured; Ferric Compounds; Ferrous Compounds; Fibroblasts; Humans; Inflammation; Male; Middle Aged; Oxidation-Reduction; Skin

An acute inflammatory response was initiated in the rabbit eye by an intravitreal injection of bacterial endotoxin. We examined the effect of topical corticosteroid therapy upon polymorphonuclear leukocyte (PMN) infiltration into the eye, protein leakage into aqueous humor and ascorbate level in aqueous humor. Corticosteroid therapy initiated prior to injection of endotoxin suppresses the clinical signs of inflammation, partially prevents the fall in aqueous-humor ascorbate level, has little effect upon protein leakage, but markedly reduces PMN infiltration. Corticosteroid therapy initiated after the injection of endotoxin also suppresses the clinical signs of inflammation, reduces the fall in ascorbate levels and does not influence protein leakage. However, in this case there is a marked persistence of PMN infiltration into ocular tissues. Thus the number of PMNs present in the ocular tissues is little different from that in non-steroid treated control eyes, although the clinical signs of inflammation are reduced. We suggest that in the clinical situation, the initial anti-inflammatory activity of the corticosteroids is related to an inhibitory effect upon the activity of PMNs already within the tissues, which then prevents the ensuing cascade of characteristic inflammatory events.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Aqueous Humor; Ascorbic Acid; Capillary Permeability; Chemotaxis, Leukocyte; Dexamethasone; Endotoxins; Eye; Eye Diseases; Eye Proteins; Female; Glucocorticoids; Inflammation; Male; Neutrophils; Prednisolone; Rabbits

The degree and the mode of association of [14C]-ascorbic acid with leucocytes are examined. The degree of association of ascorbic acid with polymorphonuclear leucocytes (1-3%) is dependent on cell type, extracellular concentration of ascorbic acid, incubation temperature, intactness of the cells and the extracellular pH. All experiments are performed according to strict protocols as these compounds are labile in aqueous solutions. Further it is noticed that in all experiments an outward gradient of leucocyte endogenic ascorbic acid exists. The results suggest that the association process comprises at least one saturable pathway. The activation of polymorphonuclear leucocytes by phorbol myristate acetate increases the accumulation of ascorbic acid threefold.

Topics: Adult; Ascorbic Acid; Biological Transport; Dehydroascorbic Acid; Glucose; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Inflammation; Neutrophils; Probenecid; Temperature

To evaluate the influence of vitamin C on pulmonary antibacterial mechanisms, normal CD-1 mice were administered sodium ascorbate (200 mg/kg/24 h) and challenged intratracheally with type 3 Streptococcus pneumoniae. Survival rates were similar in ascorbate-treated and control animals. When infected with a high inoculum (1 X 10(6) cfu), animals given vitamin C demonstrated a significant enhancement in their capacity to clear viable pneumococci from the lungs at 24 h after challenge; the augmented pulmonary clearance was associated with an increased influx of granulocytes at 6 and 24 h. After infection with a lower inoculum (1 X 10(5) cfu), animals treated with the vitamin exhibited a significant advantage in pulmonary clearance and granulocyte recruitment but at 6 h only. After a very low inoculum challenge (1 X 10(4) cfu), the clearance of viable pneumococci was retarded in ascorbate-treated mice. In vitro, the pneumococcidal capacity of resident alveolar macrophages from animals given vitamin C was significantly reduced, but the ability of these cells to generate leukocyte chemoattractant activity after stimulation with the calcium ionophore A23187 remained unaltered. We conclude that in the mouse, large doses of vitamin C alter pulmonary defense mechanisms against S. pneumoniae; however, these changes do not appear to convey a substantial advantage to the host.

Topics: Animals; Ascorbic Acid; Biomechanical Phenomena; Chemotactic Factors; Inflammation; Interleukin-8; Lung; Macrophages; Mice; Mice, Inbred Strains; Neutrophils; Pneumonia, Pneumococcal; Pulmonary Alveoli; Streptococcus pneumoniae

During an experimentally induced inflammatory response in the rabbit eye, the decrease in the ascorbic acid concentration within the aqueous humor corresponded, in large part, to the infiltration of leukocytes into this ocular fluid. Additional in vitro studies demonstrated that activated leukocytes reacted with ascorbic acid, diminishing the concentration of this vitamin in the surrounding medium. We suggest that the very high concentrations of ascorbic acid found in the aqueous humor of a number of species affords extracellular protection for the ocular tissues against oxygen radicals and metabolites released by infiltrating leukocytes during ocular inflammation.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Dose-Response Relationship, Drug; Endotoxins; Eye Diseases; Female; Hydrogen Peroxide; Inflammation; Male; Neutrophils; Oxidation-Reduction; Rabbits; Time Factors

The ocular effects of intravitreally injected copper sulfate solutions were studied in New Zealand white rabbits. These injections resulted in uveitis characterized by prolonged ocular hypotony, increased protein concentrations and decreased ascorbic acid concentrations in both the vitreous and aqueous humors, and an apparent decrease in the transport function of the anterior uvea. The extent and the duration of these effects were dose-dependent. The lower doses used, 3 or 6 micrograms of Cu as CuSO4 per eye, produced reversible inflammation. The highest dose, 30 micrograms of Cu per eye, also produced some signs of ocular chalcosis: hemorrhage, vitreous liquefaction, prolonged hypotony and local iridial ischemia. Six hours after the intravitreal injection of 6 micrograms of Cu as CuSO4 per eye, the Cu concentration in the vitreous humor increased to approximately 100 times that in the vitreous of control eyes, and began to decline only 3 days later, with a half-time of approximately 8 days. The Cu concentration in the anterior chamber of these eyes never exceeded 1 ppm and returned close to control values within 3 days. Based on these findings, factors that affect ocular trace-metal distribution and kinetics are discussed, as are reasons for the apparent difficulty in diagnosing the presence of Cu-containing intraocular foreign bodies on the basis of the Cu concentration of the aqueous humor.

Topics: Animals; Anterior Chamber; Ascorbic Acid; Copper; Copper Sulfate; Dose-Response Relationship, Drug; Eye Diseases; Eye Proteins; Female; Inflammation; Intraocular Pressure; Muscle Hypotonia; Rabbits; Time Factors; Vitreous Body

Topics: Ascorbic Acid; Humans; Inflammation; Neutrophils; Oxidation-Reduction; Superoxides

The capacity to respond to inflammatory stimuli was tested in hyperthyroid and hypothyroid rats when thyroid defects, induced by hormone administration or thyroparathyroidectomy, respectively, were fully established. Whereas hyperthyroid rats presented consistently depressed inflammatory responses, hypothyroid rats responded in a normal fashion. Decreased reactions to intracutaneously injected histamine and serotonin, inhibited swelling reaction to carrageenin, injected into one of the hind paws, and depressed primary and secondary reactions to adjuvant (heat-killed M. tuberculosis), only occurred in the hyperthyroid group. In addition, only in this group of animals enlargement of the adrenal glands, reduced content of adrenal ascorbic acid, and decreased number of circulating eosinophils, which characterize a circumstance of adrenal cortical hyperactivity, were observed. A spontaneous reversal of the acute inflammatory response of hyperthyroid animals to carrageenin occurred 3-4 days after interruption of hormone administration, and this was coincidental with the return to normal of the previously enlarged adrenal glands. Similarly, specific inhibition of adrenal cortical steroid biosynthesis in hyperthyroid rats with aminoglutethimide, restored the previously depressed response to carrageenin, without interference with the increased levels of seric thyroxin, thus suggesting that the inhibitory effects of thyroid hormones on inflammatory responses are likely to be indirect. It is concluded that an excess of circulating thyroid hormones, but not their deficiency, can impair the development of inflammatory reactions, and that this effect, at least partially, depends on an increased secretion of adrenal corticosteroids.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Aminoglutethimide; Animals; Ascorbic Acid; Histamine; Hyperthyroidism; Hypothyroidism; Inflammation; Male; Organ Size; Rats; Rats, Inbred Strains; Serotonin

Topics: Adrenal Cortex; Animals; Ascorbic Acid; Capillary Permeability; Carrageenan; Corticosterone; Edema; Eosinophils; Hindlimb; Inflammation; Insulin; Leukocyte Count; Male; Rats; Rats, Inbred Strains

At aseptic inflammation developing around a solid foreign body and proceeding both under common conditions and on the background of disturbed inactivation of free amines as a result of monoaminoxidase blockade with vetrasin or devastation of amine tissue depots with reserpine it has been stated that indices of the adrenal cortex activity (hyperemia, contents of ascorbic acid and corticoids) and those of the mast cells system in the inflammatory focus (amount of the cells, their size, contents of glycosaminoglycans, RNA, tryptophan and histidine) are subjected to certain fluctuations during inflammation. Increasing activity of the adrenal cortex fascicular zone and renewal of the mast cell population in the inflammatory focus are directly proportional to the degree of a disturbed deposition of free amines in the organism. Certain positive correlations prevail in cooperation of the adrenal cortex activity, decomposition rate of large (mature) mast cells and migration into the inflammatory focus of small (immature) forms of these cells.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Animals; Ascorbic Acid; Cell Count; Glycosaminoglycans; Inflammation; Male; Mast Cells; Monoamine Oxidase; Rats; RNA

Changes in hepatic oxidative events have been studied during extrahepatic granulomatous inflammation in the rat, together with the local anti-inflammatory effects of scavengers of reactive oxygen species. During remote localized inflammation in the rat, we observed increased hepatic lipid peroxidation and reduced hepatic levels of protecting substances such as ascorbic acid, catalase and reduced glutathione, the specific substrate for the peroxide-metabolizing enzyme, glutathione peroxidase. The levels of superoxide dismutase did not alter significantly during the period of investigation (7 days). The half-life of aminopyrine was longer in rats with a stronger inflammatory response. In addition, catalase and the anti-oxidants, alpha-tocopherol and propyl gallate, inhibited granuloma development on local injection during the acute phase inflammation. Superoxide dismutase alone was devoid of anti-inflammatory effects, but markedly enhanced the effect of catalase. Scavengers of hydroxyl radicals and of singlet oxygen failed to display anti-inflammatory activity. The results indicate that peroxides may act as mediators of inflammation and that increased lipid peroxidation is not limited to the site of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Catalase; Free Radicals; Glutathione; Granuloma; Inflammation; Liver; Male; Malondialdehyde; Propyl Gallate; Rats; Superoxide Dismutase; Vitamin E

Mononuclear cell infiltration and alteration in the connective tissues are prominent features of the inflammatory response in a number of diseases. To determine whether mononuclear cell products can modulate collagen synthesis, human peripheral mononuclear cells from normal donors were isolated by Ficoll-Hypaque gradient centrifugation and then incubated for 48 h with or without phytohemagglutinin. Confluent cultures of normal, human skin fibroblasts were incubated with [14C]proline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by [14C]hydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of [14C]proline was not significantly affected by addition of the mononuclear cell supernates, but as much as 90% decrease in the synthesis by the fibroblasts of labeled collagen was found relative to controls. Supernates from the phytohemagglutinin-stimulated cultures were more active than those from nonstimulated cells. These results suggest that mononuclear cells can synthesize a factor(s) which can selectively inhibit collagen synthesis.

Topics: Ascorbic Acid; Cell Survival; Cells, Cultured; Collagen; Culture Media; Fibroblasts; Humans; Inflammation; Lymphocytes; Microbial Collagenase; Monocytes; Protein Biosynthesis

Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

Topics: Animals; Ascorbic Acid; Diet; Fatty Acids, Nonesterified; Glucocorticoids; Humans; Immunity, Cellular; Inflammation; Lithium; Neoplasms; Nutritional Physiological Phenomena; Prostaglandins E; T-Lymphocytes; Thymus Gland; Virus Diseases; Zinc

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Fatty Alcohols; Freund's Adjuvant; Gluconates; Inactivation, Metabolic; Inflammation; Liver; Male; Mycobacterium tuberculosis; Rats; Sugar Alcohol Dehydrogenases

Topics: Animals; Arthritis, Experimental; Ascorbic Acid; Glucaric Acid; Inflammation; Liver; Male; Pentobarbital; Rats; Time Factors

Topics: Animals; Aqueous Humor; Ascorbic Acid; Ciliary Body; Dose-Response Relationship, Radiation; Eye; Inflammation; Intraocular Pressure; Iritis; Rabbits; Time Factors; X-Rays

The application into the rat conjunctiva of various phlogistic agents, such as croton oil, mustard oil and formaldehyde, elicits an increase of serum corticosterone linearly related to the log of the applied concentrations, so that from their parallelized regression lines it is possible to calculate the phlogistic potency of each tested agent in reference to croton oil. The time kinetic of such an increase (elicited by croton oil) is compared with that of two other parameters previously adopted as indirect quantitative indices of the phlogosis: the adrenal ascorbic acid depletion and the liver tyrosine-alpha-ketoglutarate transaminase increase. Serum corticosterone is shown to be the quickest and the most sensitive of the adopted indices, even if the phlogistic potency of the tested agents and the precision of these evaluations substantially coincides whatsoever the index adopted. Finally the pathways of adrenocortical activation are investigated and it is shown that the activation may be peripherally blocked by topical application of corticosteroids (but not of local anesthetics) and centrally by hypophysectomy or parenteral administration of pentobarbital plus morphine.

Topics: Administration, Topical; Adrenal Glands; Animals; Ascorbic Acid; Corticosterone; Croton Oil; Dexamethasone; Formaldehyde; Hypophysectomy; Inflammation; Liver; Male; Mepivacaine; Morphine; Mustard Plant; Pentobarbital; Plant Extracts; Plants, Medicinal; Rats; Time Factors; Tyrosine Transaminase

Imidazole, given intraperitoneally to rabbits, inhibited the prostaglandin E1-induced (PGE1) elevation of intraocular pressure. The maximum imidaz-le effect occurred at three to six hours after intraperitoneal infection. The prostaglandin E1-induced aqueous humor protein elevation was reduced markedly in the imidazole-pretreated rabbits. Intravenous administration of imidazole also was effective in reducing the intraocular pressure elevation produced by prostaglandin E1. Imidazole pretreatment by subconjunctival, subdermal, or topical routes had no such effect. Imidazole derivatives, 1-methylimidazole and 2-methylimidazole, given intraperitoneally, blocked the effect of PGE1 on intraocular pressure and aqueous humor protein. Imidazole pretreatment also inhibited the elevation of intraocular pressure produced by topical nitrogen mustard, 1 per cent.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Aqueous Humor; Ascorbic Acid; Conjunctiva; Cornea; Imidazoles; Inflammation; Injections; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Intraocular Pressure; Nitrogen Mustard Compounds; Prostaglandins E; Proteins; Rabbits; Time Factors

1 Rat paws were injected with carrageenin, and their subcutaneous tissue perfused 135 min later. These perfusates were injected intravenously into receptor rats in which they caused an attenuation of inflammatory responses. 2 The effect was not observed in adrenalectomized receptor rats nor in receptors with electrolytic lesions in the median eminence of the hypothalamus but persisted in adrenal-demedullated animals. 3 The active perfusates also induced eosinopenia in normal or adrenal-demedullated animals, but not in adrenalectomized rats, and produced an increase in blood corticosterone with a concomitant decrease in the amounts of adrenal ascorbic acid. 4 The active perfusates did not affect the responses of isolated preparations to histamine, bradykinin, prostaglandins and 5-hydroxytryptamine neither did they elicit changes of the arterial blood pressure in receptor animals. 5 The anti-inflammatory activity present in perfusates from inflamed paws seems to be formed slowly at the site of the developing inflammatory reaction, since perfusates collected 30-65 min after the injection of carrageenin were ineffective, as was plasma taken from donor rats at various time intervals after carrageenin injections. 6 It is suggested that the anti-inflammatory factor present in the active perfusates exerts its action by stimulation of the hypothalamo-pituitary-adrenal axis.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Blood Pressure; Carrageenan; Corticosterone; Edema; Eosinophils; Hypothalamus; Inflammation; Male; Pituitary Gland; Rats; Stimulation, Chemical; Time Factors; Tissue Extracts

Topics: Acute Disease; Ascorbic Acid; Ceruloplasmin; Humans; Inflammation; Seasons

Topics: Animals; Ascorbic Acid; Extracellular Space; Hexosamines; Hyaluronic Acid; Inflammation; Osmolar Concentration; Potassium; Proteins; Sodium; Staphylococcal Infections; Uronic Acids; Wounds and Injuries

Topics: Animals; Ascorbic Acid; Cobalt; Copper; Cysteine; Dactinomycin; Deferoxamine; Dinitrophenols; Edetic Acid; Fatty Liver; Fluorides; Fructose; Glucose; Glutathione; Hemochromatosis; Inflammation; Iodoacetates; Iron; Lipotropic Agents; Liver Cirrhosis; Lung; Macrophages; Microscopy, Electron; Potassium Permanganate; Protein Biosynthesis; Puromycin; Rabbits; RNA; Saponins; Sucrose; Surface-Active Agents; Transferrin; Trypsin

Topics: Adult; Aerosols; Ascorbic Acid; Bronchitis; Dermatologic Agents; Dust; Humans; Infections; Inflammation; Middle Aged; Occupational Diseases; Silicosis; Tannins

Topics: Animals; Ascorbic Acid; Autoradiography; Chromatography, Paper; In Vitro Techniques; Inflammation; Male; Mitochondria, Liver; Phosphatidylcholines; Phosphatidylethanolamines; Phosphorus Isotopes; Rats

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Hydrocortisone; Inflammation; Mice; Turpentine; Vitamin B Complex

Topics: Animals; Ascorbic Acid; Chloramphenicol; Drug Synergism; Female; Folic Acid; Inflammation; Male; Niacinamide; Penicillins; Phagocytosis; Pyridoxine; Rats; Riboflavin; Thiamine; Vitamin B 12; Vitamin K; Vitamins

Topics: 17-Hydroxycorticosteroids; Abscess; Adrenal Glands; Adrenalectomy; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Ascorbic Acid; Cholesterol; Dextrans; Edema; Formaldehyde; Granuloma; Histamine; Inflammation; Injections, Intraperitoneal; Phenylbutazone; Physiology; Rats; Serotonin; Sulfinpyrazone

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adrenalectomy; Aesculus; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Biomedical Research; Cholesterol; Edema; Escin; Guinea Pigs; Hypophysectomy; Inflammation; Lipid Metabolism; Metabolism; Pharmacology; Pituitary Gland; Rats; Research; Saponins; Tryptophan

Topics: Animals; Ascorbic Acid; Aspirin; Cyproheptadine; Edema; Flavonoids; Inflammation; Mice; Phenylbutazone; Radiometry; Research; Serotonin; Serum Albumin; Serum Albumin, Radio-Iodinated; Sodium Salicylate

Topics: Ascorbic Acid; Collagen Diseases; DNA; Eukaryota; Granulation Tissue; Granuloma; Guinea Pigs; Inflammation; Rats; Research; Silicosis; Toxicology

Topics: 17-Ketosteroids; Adrenalectomy; Ascorbic Acid; Catechols; Edema; Formaldehyde; Hyaluronoglucosaminidase; Inflammation; Pharmacology; Rats; Research; Tannins; Tea; Urine

Topics: Ascorbic Acid; Biochemical Phenomena; Biochemistry; Glycosaminoglycans; Inflammation; N-Acetylneuraminic Acid; Neuraminic Acids; Rats; Research

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Growth Hormone; Hormones; Human Growth Hormone; Humans; Inflammation; Methylprednisolone; Testosterone; Testosterone Congeners

Topics: Ascorbic Acid; Cataract; Dehydroascorbic Acid; Disease; Eye; Humans; Inflammation; Uvea

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Ascorbic Acid; Biological Transport; Carbohydrate Metabolism; Inflammation; Vitamins

Topics: Ascorbic Acid; Cholesterol; Hematologic Diseases; Humans; Inflammation; Lipid Metabolism Disorders; Vitamins

Topics: Acute Disease; Ascorbic Acid; Calcium; Calcium, Dietary; Humans; Inflammation; Pyrrolidinones; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Deficiency Diseases; Guinea Pigs; Humans; Inflammation; Periodontitis; Periodontium; Vitamins