ascorbic-acid and Lung-Diseases

On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.

Topics: Adiponectin; Antioxidants; Ascorbic Acid; Betacoronavirus; Coronavirus Infections; COVID-19; Diet; Dietary Supplements; Fatty Acids, Omega-3; Flavonoids; Humans; Interleukin-6; Lung Diseases; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tumor Necrosis Factor-alpha

Chlorine (Cl(2)) is a reactive oxidant gas used extensively in industrial processes. Exposure of both humans and animals to high concentrations of Cl(2) results in acute lung injury, which may resolve spontaneously or progress to acute respiratory failure. Injury to airway and alveolar epithelium may result from chemical reactions of Cl(2), from HOCl (the hydrolysis product of Cl(2)), and/or from the various reaction products, such as chloramines, that are formed from the reactions of these chlorinating species with biological molecules. Subsequent reactions may initiate self-propagating reactions and induce the production of inflammatory mediators compounding injury to pulmonary surfactant, ion channels, and components of lung epithelial and airway cells. Low-molecular-weight antioxidants, such as ascorbate, glutathione, and urate, present in the lung epithelial lining fluid and tissue, remove Cl(2) and HOCl and thus decrease injury to critical target biological targets. However, levels of lung antioxidants of animals exposed to Cl(2) in concentrations likely to be encountered in the vicinity of industrial accidents decrease rapidly and irreversibly. Our measurements show that prophylactic administration of a mixture containing ascorbate and desferal N-acetyl-cysteine, a precursor of reduced glutathione, prevents Cl(2)-induced injury to the alveolar epithelium of rats exposed to Cl(2). The clinical challenge is to deliver sufficient quantities of antioxidants noninvasively, after Cl(2) exposure, to decrease morbidity and mortality.

Topics: Acetylcysteine; Animals; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Chlorine; Gases; Inhalation Exposure; Lung; Lung Diseases; Models, Animal; Rabbits; Rats

Topics: Administration, Inhalation; Ascorbic Acid; beta Carotene; Cystic Fibrosis; Humans; Lung Diseases; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Sulfhydryl Compounds; Trachea

Topics: Air Pollution; Ascorbic Acid; Free Radicals; Glutathione; Humans; Lipid Peroxidation; Lung Diseases; Models, Biological; Oxidation-Reduction; Ozone

Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age.. To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes.. Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing.. The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs.. We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.

Topics: Adult; Ascorbic Acid; Dietary Supplements; DNA Methylation; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Lung Diseases; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Smoking

Pressure ulcers are a significant burden in the ICU. Many factors have found to be associated with pressure ulcers including malnutrition. While it has been recognized that high protein diets decrease the incidence of pressure ulcers, the role of lipids as well as vitamins and antioxidants remains unclear. The aim of this study was to evaluate the preventive and healing effects of an enteral diet enriched in eicosapentanoic acid (EPA) and gamma-linolenic acid (GLA) and vitamins (vitamins A, C and E) on pressure ulcers.. One hundred patients with acute lung injury were included in a larger study evaluating the effects of lipids and vitamins on respiratory function. A secondary end point, occurrence and healing of pressure ulcers was included. A diet enriched in lipids (EPA, GLA) and vitamins (vitamins A, C and E) was compared with a diet similar in macronutrient composition. The occurrence and healing of pressure ulcers was evaluated according to the National Pressure Ulcer Panel. Nutritional assessment included calorie intake, resting energy expenditure, levels of serum prealbumin, albumin, vitamins A and E, zinc and copper. C-reactive protein and procalcitonin were also measured.. Patient's age, severity of disease and gender distribution were similar in the two groups. The study group had a higher body mass index. At baseline, the pressure ulcer score was similar in the two groups A significantly lower rate of occurrence of new pressure ulcers was observed in the study group compared to the control group (p<0.05). No difference was observed in the healing of existing pressure ulcers in the study as opposed to the control group. There was no significant difference in the nutritional parameters between the two groups.. A diet enriched with EPA, GLA and vitamins A, C and E is associated with a significantly lower occurrence of new pressure ulcers in critically ill patients with acute lung injury.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Chi-Square Distribution; Critical Illness; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Lung Diseases; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Pressure Ulcer; Prospective Studies; Respiration, Artificial; Severity of Illness Index; Treatment Outcome; Vitamin A; Vitamin E; Vitamins; Wound Healing

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

In 14 patients in the age of 55 to 72 years (mean 60,5 years) with chronic nonspecific lung disease the long lasting effect of the "oxygen-multistep-therapy" are arterial oxygen pressure (paO2) has been proved. By the applied regimen of "O2-multistep-sleeping" after a cumulative O2-application-time of 56 hours mean paO2 of 68,1 Torr did not improve significantly.

Topics: Aged; Ascorbic Acid; Dipyridamole; Female; Humans; Isosorbide Dinitrate; Lung Diseases; Male; Middle Aged; Orotic Acid; Ouabain; Oxygen; Oxygen Inhalation Therapy; Partial Pressure; Sleep; Thiamine

Topics: A549 Cells; Alginates; Animals; Antioxidants; Ascorbic Acid; Biological Transport; Cell Line; Cell Line, Tumor; Chitosan; Drug Carriers; Drug Delivery Systems; Female; Humans; Lung; Lung Diseases; Macrophages, Alveolar; Male; Nanoparticles; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rats; Rats, Wistar; Respiratory Mucosa; Rifampin; Swine; Tissue Distribution

The pathogenesis and progression of several lung disorders is propagated by inflammatory and oxidative processes, which can be controlled by adjunctive inhaled therapies. The present study aimed to develop an inhalable dry powder formulation consisting of co-spray-dried urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate (SD HA-CL-SAP), a novel combination which was recently shown to possess anti-inflammatory, antioxidant, and wound healing properties. Native HA and SAP were co-spray dried (SD HA-SAP) and evaluated as control formulation. Yield (Y%) and encapsulation efficiency (EE%) were 67.0 ± 4.8% and 75.5 ± 7.2% for SD HA-SAP, 70.0 ± 1.5% and 66.5 ± 5.7% for SD HA-CL-SAP, respectively. Both formulations were shown to be suitable for lung delivery in terms of morphology, particle size (median volumetric diameter ∼ 3.4 μm), physical and thermal stability, in vitro aerosol performance - respirable fraction: 30.5 ± 0.7% for SD HA-SAP and 35.3 ± 0.3% for SD HA-CL-SAP. SAP release was investigated using Franz cells and air-interface Calu-3 cell model (>90% of SAP transported within 4 h). The innovative SD HA-CL-SAP formulation holds potential as inhalable dry powder for the treatment of inflammatory lung disorders.

Topics: Administration, Inhalation; Aerosols; Anti-Inflammatory Agents; Ascorbic Acid; Cell Line, Tumor; Chemistry, Pharmaceutical; Cross-Linking Reagents; Desiccation; Drug Combinations; Drug Compounding; Drug Stability; Dry Powder Inhalers; Humans; Hyaluronic Acid; Lung Diseases; Particle Size; Powders; Urea

Garlic capsule (GAR) and/or selenium- vitamin A, C, E (S-VACE) might be useful in the treatment of lung diseases. The present study evaluated the toxicity of lisinopril (LIS) in the lungs of male rats and the reversal effect of GAR and/or selenium-vitamins A, C, and E (S-VACE).. Group I served as the control, whereas animals in groups II, III, IV, and V received 28 mg of LIS/kg body weight by gavage. Group III was co-treated with GAR at a therapeutic dosage of 250 mg/kg body weight per day. Group IV was co-treated with S-VACE at dosage of 500 mg/kg body weight per day. Lastly, group V was co-treated with GAR and S-VACE at dosages of 250 and 500 mg/kg body weight per day, respectively. The experiment lasted for 8 days (sub-acute exposure).. Administration of therapeutic dose of LIS to male rats depleted enzymatic antioxidants (superoxide dismutase and catalase) and cellular adenosine triphosphate content with concomitant increase in lipid peroxidation. Histopathology examination showed damage to the epithelial cells of the airways. These effects were prevented by both single and combination treatment of GAR and S-VACE in male rats with LIS-induced lung toxicity.. We therefore concluded that the combination of GAR and S-VACE can be a novel therapy for the management of lung diseases in humans.

Topics: Adenosine Triphosphate; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Garlic; Lipid Peroxidation; Lisinopril; Lung Diseases; Male; Rats; Rats, Wistar; Respiratory Mucosa; Selenium; Vitamin A; Vitamin E; Vitamins

To analyze the regularity in combined medication with Xiyanping injection (Xiyanping for short) in the real world by as- sociation rules. Totally 5 822 patients using Xiyanping injection was collected from the 18 Class III Grade I hospitals nationwide to study the combined medication information of the patient with lung infection and make the analysis by using association rules and Apriori. According to the results, major drugs combined with Xiyanping in treatment of lung infection included compound amino acid, inosine, coenzyme A, cytidine triphosphate, vitamin C. Common drugs combined with Xiyanping can be divided into 5 categories: nutrition support therapy (vitamin C, compound amino acid) , coenzymes (coenzyme A, cytidine triphosphate, inosine), expectorants and antiasthmatics (ambroxol, salbutamol, doxofylline), hormones (dexamethasone, budesonide), antibiotics (mainly cefminox). The main combined medicines mostly conformed to the regularity for drugs treating lung infection. In addition, there were two most common medical combination models: the model for Xiyanping combined a single medicine is Xiyanping + nutrition support therapy, while the model for Xiyanping combined two or more than two medicines is Xiyanping + nutrition support therapy + coenzyme. Pharmacologically, Xiyanping is mostly combined with western medicines with similar pharmacological effects to substitute or supplement the antibiotic effect in treating lung infection. However, further studies shall be conducted for the safety and rationality of the combined medication based on clinical practices, in order to provide reference for clinical medication.

Topics: Adult; Anti-Bacterial Agents; Ascorbic Acid; Cephamycins; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Hospital Information Systems; Humans; Lung Diseases; Male; Middle Aged; Young Adult

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

To determine the efficiency of selenium and/or vitamin E to alleviate lung oxidative damage induced by dimethoate, an organophosphorus compound.. Adult Wistar rats were exposed during 30 days either to dimethoate (0.2 g/L of drinking water), dimethoate+selenium (0.5 mg/kg of diet), dimethoate+vitamin E (100 mg/kg of diet), or dimethoate+selenium+vitamin E.. Exposure to dimethoate caused oxidative stress in lung evidenced by an increase of malondialdehyde, protein carbonyl groups and advanced oxidation protein products. An increase in glutathione peroxidase, superoxide dismutase, catalase and a decrease in acetylcholinesterase and butyrylcholinesterase activities, glutathione, non-protein thiols and vitamins C levels were observed. Histopathological changes in lung tissue were noted as emphysema, hemorrhages and hemosiderin deposits. Co-administration of selenium or vitamin E to the diet of dimethoate treated rats ameliorated the biochemical parameters as well as histological impairments. The joint effect of these elements was more powerful in antagonizing dimethoate-induced lung oxidative damage.. We concluded that selenium and vitamin E ameliorated the toxic effects of this pesticide in lung tissue suggesting their role as potential antioxidants.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Butyrylcholinesterase; Dimethoate; Glutathione; Lipid Peroxidation; Lung Diseases; Oxidative Stress; Rats; Rats, Wistar; Selenium; Vitamin E

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on growth and the cardiovascular system. Glucocorticoid excess promotes free radical overproduction and vascular dysfunction.. We hypothesized that the adverse effects of postnatal glucocorticoid therapy are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects.. Male rat pups received a clinically relevant course of dexamethasone (Dex), or Dex with vitamins C and E (DexCE), on postnatal days 1-6 (P1-6). Controls received saline (Ctrl) or saline with vitamins (CtrlCE).. At P21, Dex reduced survival (Ctrl: 96 vs. Dex: 70%) and promoted asymmetric growth restriction (ponderal index, Ctrl: 6.3 +/- 0.1 g . mm(-3) x 10(-5) vs. Dex: 7.4 +/- 0.2 g . mm(-3) x 10(-5)), both p < 0.05. Dex increased cardiac oxidative stress (protein expression: 4-HNE +20%, Hsp90 -42% and eNOS -54%), induced left ventricle (LV) wall thinning (LV wall volume: Ctrl: 47.2 +/- 1.2 mm(3) vs. Dex: 38.9 +/- 1.7 mm(3)) and decreased the ratio of the aortic lumen:total vessel area (Ctrl: 0.74 +/- 0.01 vs. Dex: 0.66 +/- 0.02), all p < 0.05. DexCE restored towards control values survival, growth symmetry the aortic lumen:total vessel area, and increased the cardiac expression of Hsp90 relative to Dex. In addition, relative to controls, the decrease in the cardiac expression of eNOS was no longer significant in DexCE animals (-20.3 +/- 14.4%, p > 0.05). However, DexCE did not prevent growth retardation, cardiac 4-HNE upregulation (DexCE: +29%) or LV thinning (DexCE: 40.1 +/- 1.1 mm(3)). Treatment of neonates with vitamins alone affected somatic growth and promoted thinner LV walls (CtrlCE: 39.9 +/- 0.5 mm(3), p < 0.05).. Combined glucocorticoid and antioxidant therapy in premature infants may be safer than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.

Topics: Aldehydes; Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Chronic Disease; Dexamethasone; Drug Therapy, Combination; Glucocorticoids; Heart; HSP90 Heat-Shock Proteins; Lung Diseases; Male; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Vitamin E

Many studies suggest a role for antioxidants in the prevention of lung hypoplasia in nitrofen-induced rat models with congenital diaphragmatic hernia (CDH). This study investigates the oxidative status and the histological outcome of prenatal administration of vitamins E and C with synergistic effect, and effect of N-acetylcysteine (NAC) to improve lung maturation of nitrofen-induced rats.. CDH was induced by maternal administration of a single oral dose of nitrofen on day 9.5 of gestation, and the Sprague-Dawley rats were randomly divided into five groups: nitrofen (N), nitrofen + vitamin C (NC), nitrofen + vitamin E (NE), nitrofen + vitamin C + vitamin E (NCE) and nitrofen + NAC (NNAC). A control group in which only vehicle was administered was included. Cesarean section was performed on day 21. Body weight (BW) and total lung weight (LW) of all fetuses with CDH were recorded; lung histological evaluation was performed, and protein content of lungs, determination of thiobarbituric acid reactive substances, and the protein carbonyls in tissue samples were determined.. A total of 133 rat fetuses with CDH were investigated. The body weight and the lung weight of fetuses of all groups that were exposed to nitrofen were significantly decreased than of the control group (P < 0.05). The animals exposed to nitrofen with different antioxidants showed increased protein levels in lung tissue. However, in the NCE and the NNAC groups, protein levels were significantly increased than in the others. Malondialdehyde levels significantly decreased in the NCE and the NNAC groups when compared with the NC and the NE groups. In addition, the NCE and NNAC groups decreased protein oxidation to control levels, and no significant difference was observed between control and these two antioxidants groups. The N, NC, NE and NNAC groups showed minimal improvement in lung histology; the NCE groups showed the most improvement in lung histology when compared with the other nitrofen plus antioxidant groups.. Prenatal administration of NAC and vitamin E in combination with vitamin C represented the best effects to avoid oxidative damage and protein content of the lungs in rat pups with CDH at birth.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Drug Synergism; Female; Fetus; Free Radical Scavengers; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Lipid Peroxidation; Lung; Lung Diseases; Male; Maternal-Fetal Exchange; Pesticides; Phenyl Ethers; Pregnancy; Proteins; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances; Vitamin E

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

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

The effect of cigarette smoke exposure on lungs of rat pups was evaluated. Animals were exposed to passive cigarette smoke during 3 weeks and a number of toxicological parameters in lung of pups were examined, such as lipid peroxidation, delta-aminolevulic acid dehydratase (delta-ALA-D) activity, components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non-protein thiol (NPSH) levels). Furthermore, a possible protective effect of diphenyl diselenide, (PhSe)(2), was studied. The results demonstrated an increase in lipid peroxidation, an inhibition of delta-ALA-D activity, a reduction of Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage in lungs of rat pups. Oral administration of (PhSe)(2) (0.5mg/kg) restored TBARS levels, non-enzymatic antioxidant defenses and activity of delta-ALA-D. These results indicated that exposure to cigarette smoke enhanced oxidative stress, thereby disturbing the tissue defense system. (PhSe)(2) protected against oxidative damage induced by cigarette smoke exposure in lung of rat pups.

Topics: Aminolevulinic Acid; Animals; Animals, Suckling; Antioxidants; Ascorbic Acid; Benzene Derivatives; Body Weight; Catalase; Female; Lipid Peroxidation; Lung Diseases; Male; Organoselenium Compounds; Pregnancy; Rats; Rats, Wistar; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tobacco Smoke Pollution

Exposure of mice to single-walled carbon nanotubes (SWCNTs) induces an unusually robust pulmonary inflammatory response with an early onset of fibrosis, which is accompanied by oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system, specifically vitamin E, the major lipid-soluble antioxidant, in the SWCNT-induced reactions has not been characterized. We used C57BL/6 mice, maintained on vitamin E-sufficient or vitamin E-deficient diets, to explore and compare the pulmonary inflammatory reactions to aspired SWCNTs. The vitamin E-deficient diet caused a 90-fold depletion of alpha-tocopherol in the lung tissue and resulted in a significant decline of other antioxidants (GSH, ascorbate) as well as accumulation of lipid peroxidation products. A greater decrease of pulmonary antioxidants was detected in SWCNT-treated vitamin E-deficient mice as compared to controls. Lowered levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity to SWCNT-induced acute inflammation (total number of inflammatory cells, number of polymorphonuclear leukocytes, released LDH, total protein content and levels of pro-inflammatory cytokines, TNF-alpha and IL-6) and enhanced profibrotic responses (elevation of TGF-beta and collagen deposition). Exposure to SWCNTs markedly shifted the ratio of cleaved to full-length extracellular superoxide dismutase (EC-SOD). Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies.

Topics: Animals; Antioxidants; Ascorbic Acid; Cytokines; Female; Foreign-Body Reaction; Glutathione; Lipid Peroxidation; Lung Diseases; Mice; Mice, Inbred C57BL; Nanotubes, Carbon; Oxidative Stress; Particulate Matter; Superoxide Dismutase; Vitamin E Deficiency

This study was designed to examine if diphenyl diselenide (PhSe)(2), an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl(2). Male adult Swiss albino mice received CdCl(2) (10 micromol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe)(2) (10 micromol/kg or 20 micromol/kg, orally) was given concomitantly with CdCl(2) to mice. A number of toxicological parameters in lung and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na(+),K(+)-ATPase activity, acetylcholinesterase (AChE) activity, [(3)H]glutamate uptake and [(3)H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe)(2) at the dose of 20 micromol/kg protected the inhibition of delta-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl(2) in lungs. At 10 micromol/kg, (PhSe)(2) protected cerebral AChE and CAT activities inhibited by CdCl(2). There were no histopathological alterations in the lung of mice after CdCl(2) exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl(2) than in control mice. (PhSe)(2) at dose of 20 micromol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe)(2) attenuated the oxidative damage induced by CdCl(2) in lung and brain of mice.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Brain Diseases; Cadmium Chloride; Catalase; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamic Acid; Lipid Peroxidation; Lung; Lung Diseases; Male; Mice; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Sodium-Potassium-Exchanging ATPase; Sulfhydryl Compounds; Superoxide Dismutase

Oxidant herbicide nitrofen (2,4-dichloro-4'-nitrodiphenyl ether) induces in rat embryos congenital diaphragmatic hernia (CDH) with lung hypoplasia. The present study aims at examining whether antioxidant vitamins A, E, and C reverse the effects of the teratogen in the lungs of exposed rats and how they modify the expression of molecular regulators known to be involved in their pathogenesis.. Wet lung weight-body weight ratio, total DNA, and total protein were determined. Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3beta (HNF-3beta), and surfactant protein B (SP-B) proteins were measured by immunoblot assay in lung homogenates from rat fetuses exposed in utero to either nitrofen 100 mg intragastrically or vehicle. The coexpression of these factors in the alveolar epithelium was demonstrated by immunohistochemistry. The effects of the addition of vitamins A, C, and E were assessed by comparison with analysis of variance.. Nitrofen decreased lung weight, total DNA, and total protein. The addition of antioxidant vitamins had no effect on lung weight, but increased DNA and protein contents. TTF-1, HNF-3beta, and SP-B proteins were decreased in lung homogenates of exposed rats with CDH. The addition of antioxidant vitamins nearly normalized these values.. The effects of nitrofen in fetal rat lungs are reversed in part by antioxidant vitamins by upregulating the expression of TTF-1, HNF-3beta, and SP-B. This approach could help to develop transplacental prenatal interventions for CDH.

Topics: Animals; Antioxidants; Ascorbic Acid; Female; Hepatocyte Nuclear Factor 3-beta; Herbicides; Hernia, Diaphragmatic; Lung; Lung Diseases; Nuclear Proteins; Organ Size; Peptide Fragments; Phenyl Ethers; Pregnancy; Proteolipids; Rats; Rats, Sprague-Dawley; Respiratory System Abnormalities; Thyroid Nuclear Factor 1; Transcription Factors; Up-Regulation; Vitamin A; Vitamin E; Vitamins

We studied the effect of oral supplementation with L-ascorbic acid (50 mg /100 g body weight (BW) on nickel sulfate (2.0 mg/ 100 g BW, i.p)-induced lipid peroxidation and histopathology in the lung of Wister strain male albino rats. Lipid peroxide and glutathione levels and the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), were estimated. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased all antioxidant enzyme activities. Nickel sulfate treatment also induced (a) loss of normal characteristics and architectural organization, (b) inflammation in bronchioles, (c) alveolar congestion, (d) alveolar cell hyperplasia, and (e) congestion in the lumen. The simultaneous administration of L-ascorbic acid and nickel sulfate improved both lipid peroxidation and the histopathology of lung when compared with rats receiving nickel sulfate alone. The results indicate that L-ascorbic acid prevents nickel-induced alteration of antioxidant defense mechanisms and histopathology of lung tissue.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Glutathione Peroxidase; Lipid Peroxidation; Lung; Lung Diseases; Male; Necrosis; Nickel; Paraffin Embedding; Rats; Rats, Wistar; Superoxide Dismutase

Light-exposed parenteral multivitamins induce in lungs peroxide-like oxidant responses as well as the initiation of fibrosis. We hypothesized that peroxides generated in light-exposed total parenteral nutrition (TPN) affect lung remodeling. The objective was to assess the specific roles of peroxides, multivitamin preparation (MVP), and light exposure on lung remodeling during TPN. Three-day-old guinea pigs fitted with an indwelling catheter were assigned to the following intravenous regimens: TPN or MVP +/- photoprotection, H(2)O(2)+/- glutathione, MVP +/- metabisulfite, or ascorbic acid +/- riboflavin. Fed animals served as controls. After 4 days, lungs were sampled to determine alveolarization (intercepts), beta-actin mRNA (protection assay), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Data were analyzed by analysis of variance. The infusion of light-exposed multivitamins induced a 20% lower (p < 0.01) alveolarization index than fed controls, and 3-fold higher (p < 0.01) apoptotic events. This was prevented by photoprotecting TPN. The effect of multivitamins on the alveolarization index was reproduced (p < 0.05) by infusion of light-exposed riboflavin in the presence of vitamin C. The alveolarization index correlated (r(2) = 0.35; p < 0.05) with beta-actin mRNA, suggesting alveolar disruption. Antiperoxides conferred no protection against decreased alveolarization. Lung remodeling induced by exposure of TPN to ambient light is not due to a direct effect of infused peroxides but rather to an interaction between vitamin C and peroxides generated by the exposure of riboflavin to light. It is speculated that this interaction may play a role in the development of chronic lung disease of premature infants who receive TPN and have immature antioxidant defenses.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Drug Interactions; Guinea Pigs; Light; Lung Diseases; Riboflavin

Antioxidants have been shown to be effective in attenuating acute lung injury. In this study, we determine the effects of various antioxidants by different mechanisms on the lipopolysaccharide (LPS)-induced changes. LPS was administered intravenously at a dose of 10 mg/kg to anesthetized rats. LPS induced a significant decrease in blood pressure (P < 0.01) and increased exhaled nitric oxide (NO) from 3.60+/-0.18 to 35.53+/-3.23 ppb (P < 0.01) during an observation period of 4 h. Plasma nitrate concentrations also increased from 0.61+/-0.06 to 1.54+/-0.22 micromol/l (P < 0.05). LPS-induced oxygen radical release from white blood cells isolated from rat peripheral blood also increased significantly (P < 0.001). After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and manganese superoxide dismutase (MnSOD). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta, TNF-alpha and MnSOD were absent. Four hours after LPS administration, mRNA expressions of iNOS, IL-1beta, and MnSOD were significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial cell damage and interstitial edema. Various antioxidants were given 1 h after LPS administration. These agents include SOD, catalase (CAT), SOD + CAT or vitamin C (ascorbic acid). These antioxidants effectively reversed the systemic hypotension, reduced the quantity of exhaled NO and plasma nitrate concentration, and prevented acute lung injury. Administration of various antioxidants also significantly attenuated LPS-induced oxygen radical release by rat white blood cells. LPS induced mRNA expressions of MnSOD and iNOS were significantly depressed by these antioxidants. However, only SOD + CAT and vitamin C inhibited the mRNA expression of IL-1beta. These results suggest that oxygen radicals are responsible for LPS-induced lung injury. Antioxidants can attenuate the lung injury by inhibiting mRNA expressions of iNOS and IL-1beta.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Catalase; Endotoxins; Exhalation; Gene Expression; Interleukin-1; Lipopolysaccharides; Luminescent Measurements; Lung; Lung Diseases; Male; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Osmolar Concentration; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Inhaled urban particulate matter (PM) often contains metals that appear to contribute to its toxicity. These particles first make contact with a thin layer of epithelial lining fluid in the respiratory tract. Antioxidants present in this fluid and in cells might be important susceptibility factors in PM toxicity. We investigated the role of ascorbic acid (C) and glutathione (GSH) as determinants of susceptibility to inhaled residual oil fly ash (ROFA) in guinea pigs (male, Hartley). Guinea pigs were divided into four groups, +C+GSH, +C-GSH, -C+GSH, and -C-GSH, and exposed to clean air or ROFA (< 2.5 micron diameter, 19--25 mg/m(3) nose-only for 2.0 h). C and/or GSH were lowered by either feeding C-depleted diet (1 microg C/kg diet, 2 weeks) and/or by ip injection of a mixture of buthionine-S,R-sulfoximine (2.7 mmol/kg body weight) and diethylmaleate (1.2 mmol/kg, 2 h prior). Nasal lavage (NL) and bronchoalveolar lavage (BAL) fluid and cells were examined at 0 h and 24 h postexposure to ROFA. The C-deficient diet lowered C concentrations in BAL fluid and cells and in NL fluid by 90%, and the GSH-depletion regimen lowered both GSH and C in the BAL fluid and cells by 50%. ROFA deposition was calculated at time 0 from lung Ni levels to be 46 microg/g wet lung. In unexposed animals, the combined deficiency of C and GSH modified the cellular composition of cells recovered in lavage fluid, i.e., the increased number of eosinophils and macrophages in BAL fluid. ROFA inhalation increased lung injury in the -C-GSH group only (evidenced by increased BAL protein, LDH and neutrophils, and decreased BAL macrophages). ROFA exposure decreased C in BAL and NL at 0 h, and increased BAL C and GSH (2- to 4-fold above normal) at 24 h in nondepleted guinea pigs, but had no effect on C and GSH in depleted guinea pigs. Combined deficiency of C and GSH resulted in the highest macrophage and eosinophil counts of any group. GSH depletion was associated with increased BAL protein and LDH, increased numbers of BAL macrophages and eosinophils, and decreased rectal body temperatures. We conclude that combined deficiency of C and GSH increased susceptibility to inhaled ROFA; caused unusual BAL cellular changes; resulted in lower antioxidant concentrations in BAL than were observed with single deficiencies. Antioxidant deficiency may explain increased susceptibility to PM in elderly or diseased populations and may have important implications for extrapolating animal toxicity data to huma

Topics: Administration, Inhalation; Air Pollutants; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Temperature; Bronchoalveolar Lavage Fluid; Carbon; Cell Count; Coal Ash; Disease Models, Animal; Eosinophils; Glutathione; Guinea Pigs; L-Lactate Dehydrogenase; Lung; Lung Diseases; Macrophages, Alveolar; Male; Nasal Lavage Fluid; Neutrophils; Particle Size; Particulate Matter; Survival Rate; Time Factors; Uric Acid

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24-36 wk gestation; 5 term, 37-39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1-3, 4-6, and 7-9, Kruskal-Wallis ANOVA: P = 0.016, P < 0.0001, and P = 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1-3 and 4-6 (P = 0.005 and P = 0.044) compared with term babies. Very preterm babies (24-28 wk gestation) had increased concentrations of protein carbonyls at days 4-6 (P = 0.056) and significantly decreased ascorbate concentrations at days 4-6 (P = 0.004) compared with preterm babies (29-36 wk gestation). Urate concentrations were significantly elevated at days 1-3 (P = 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Chronic Disease; Female; Humans; Infant, Newborn; Infant, Premature; Lung; Lung Diseases; Male; Oxidation-Reduction; Oxidative Stress; Proteins; Respiration, Artificial; Risk Factors; Treatment Outcome; Uric Acid

Nephrocalcinosis (NC) in preterm neonates has been described frequently, and small-scale studies suggest an unfavorable effect on renal function. The etiologic factors have not yet been fully clarified. We performed a prospective observational study to identify factors that influence the development of NC.. The study population consisted of 215 preterm neonates with a gestational age <32 weeks. Clinical characteristics and intake in the first four weeks of calcium, phosphorus, vitamin D, protein, and ascorbic acid were noted. Serum calcium, phosphate, vitamin D, magnesium, uric acid, creatinine, urea and urinary calcium, phosphate, oxalate, citrate, magnesium, uric acid, and creatinine were assessed at four weeks of age and at term. Renal ultrasonography (US) was performed at four weeks and at term. At term was defined as a postconceptional age of 38 to 42 weeks.. NC was diagnosed by means of US in 33% at four weeks and in 41% at term. Patients with NC at four weeks had a significantly higher mean intake of calcium (P < 0.05), phosphorus (P < 0.05), and ascorbic acid (P < 0.01) than patients without NC. They had a higher mean serum calcium (2.55 vs. 2.46 mmol/L, P < 0.01) and a higher mean urinary calcium/creatinine ratio (2.6 vs. 2.1 mmol/mmol, P < 0.05). Patients with NC at term had a lower birth weight (1142 vs. 1260 g, P < 0.05) and a lower gestational age (28.8 vs. 29.4 weeks, P < 0.05), were treated significantly longer with furosemide, dexamethasone, theophylline, and thiazides, developed chronic lung disease more frequently (40 vs. 16%, P < 0.001), and had a higher mean urinary calcium/creatinine ratio (2.7 vs. 2.3 mmol/mmol, P < 0.05) and a lower mean urinary citrate/calcium ratio (1.1 vs. 1.7 mmol/mmol, P = 0.005).. NC develops as a result of an imbalance between stone-inhibiting and stone-promoting factors. A high intake of calcium, phosphorus, and ascorbic acid, a low urinary citrate/calcium ratio, a high urinary calcium/creatinine ratio, immaturity, and medication to prevent or treat chronic lung disease with hypercalciuric side effects appear to contribute to the high incidence of NC in preterm neonates.

Topics: Ascorbic Acid; Birth Weight; Calcium; Chronic Disease; Citrates; Creatinine; Gestational Age; Humans; Infant Food; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Lung Diseases; Nephrocalcinosis; Phosphorus; Prospective Studies; Ultrasonography; Urine

Acute exposure of rats to acrolein (1 or 2 ppm) resulted in reduced levels of glutathione, ascorbic acid and alpha-tocopherol. The activities of catalase and glutathione peroxidase were reduced whereas an increase in the activities of superoxide dismutase was observed. This led to enhanced lipid peroxidation, which produced extensive lung damage as indicated by the elevated levels of the biochemical markers--angiotensin converting enzyme, lactate dehydrogenase, protein and lactate in the bronchoalveolar lavage.

Topics: Acrolein; Acute Disease; Animals; Ascorbic Acid; Glutathione; Lipid Peroxidation; Lung; Lung Diseases; Male; Oxidation-Reduction; Rats; Rats, Wistar; Sulfhydryl Compounds; Vitamin E

Allantoin, the oxidation product of uric acid (UA), can be used as an in vivo marker of free radical generation. The aims of the present study were to evaluate the allantoin changes in plasma and bronchoalveolar lavage fluid (BALF) as well as to examine plasma levels of ascorbic acid (AA) and its oxidation product, dehydroascorbic acid (DHAA), in infants with or without chronic lung disease (CLD) during the first week of life. The study population was 20 infants of 24-30 weeks gestation, comprising 10 who subsequently developed CLD and 10 without CLD. In the CLD infants, the plasma allantoin/UA ratio showed a significant increase after day 1 and continued to increase gradually to reach a peak on day 6 (6.5 +/- 4.1% for CLD and 2.1 +/- 0.9% for non-CLD infants). The allantoin/UA ratio in BALF was also higher in CLD infants and the difference reached significance on days 4-6 (41.2 +/- 15.8% for CLD and 11.7 +/- 9.9% for non-CLD infants). In contrast to allantoin, the plasma DHAA/AA ratio did not differ between the 2 groups throughout the study period. Our findings that the allantoin/UA ratios were significantly higher in CLD than non-CLD infants not only in plasma but also in BALF, and that the intergroup differences of this ratio in both plasma and BALF was more prominent in the latter half of the first week of life further confirm our previous speculation that oxygen radicals are involved in the development of neonatal CLD.

Topics: Allantoin; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Chronic Disease; Cohort Studies; Dehydroascorbic Acid; Female; Free Radicals; Humans; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases; Male; Oxidation-Reduction; Uric Acid

Vitamin C, a potent antioxidant, can act as a pro-oxidant in the presence of free transition metal ions by accelerating the Fenton reaction. An in vivo pro-oxidant role of vitamin C has been suggested, but direct evidence for it is scant. Here, we report the dual role of vitamin C on paraquat-induced lung injury, which appears to depend on the metal ions released from damaged cells. Vitamin C (10 mg/kg) given at the time when the extensive tissue damage was in progress aggravated the oxidative damage, while it protected against the damage when given before the initiation of the damage. The extent of oxidative tissue damage was monitored by measuring the expiratory ethane, one of the hydrocarbons produced during lipid peroxidation. Deferoxamine, given intraperitoneally as a bolus dose of 50 mg/kg, completely blocked the aggravation of oxidative damage by vitamin C. Moreover, deferoxamine unmasked the antioxidant effect of vitamin C. The results show that vitamin C can either aggravate or alleviate the oxidative tissue damage depending on the presence of metal ions released from damaged cells.

Topics: Animals; Ascorbic Acid; Breath Tests; Deferoxamine; Ethane; Lipid Peroxidation; Lung; Lung Diseases; Male; Metals; Oxidation-Reduction; Paraquat; Proteins; Rats; Rats, Sprague-Dawley

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

This study compared plasma redox ratios of uric acid and ascorbic acid in well preterm babies with those with respiratory distress syndrome (RDS) and chronic lung disease (CLD), and investigated the relationship between these ratios and their respective measurements in tracheal aspirate. On day 1 after birth, plasma allantoin and allantoin/uric acid ratio were elevated in CLD (p < .05), and both markers of oxidative stress enabled early prediction of development of CLD (sensitivity and specificity: 54 and 83%, respectively). The relation between allantoin production and oxidative stress is supported by the correlation between the allantoin level and oxygen therapy in both RDS and CLD (p < .05). Reduced and oxidize ascorbic acid in plasma decreased postnatally in all groups and their redox ratio remained stable. Uric acid and ascorbic acid redox ratios were significantly elevated in tracheal aspirates compared to plasma samples (p < .05), and there was a strong positive correlation between both ratios (p < .005). These markers may be useful in monitoring babies with respiratory distress.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Case-Control Studies; Chronic Disease; Free Radicals; Humans; Infant, Newborn; Infant, Premature; Lung Diseases; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Respiratory Distress Syndrome, Newborn; Suction; Trachea; Uric Acid

The aim of this study was to determine whether a relationship exists between the circulating concentration of antioxidants, or markers of oxidative stress, and pulmonary function in cystic fibrosis patients. Plasma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidation) and protein carbonyls (protein oxidation). Antioxidant status was determined from the plasma concentrations of alpha-tocopherol, ascorbic acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow (FEF25-75) were measured in 25 of the subjects by spirometry, and expressed as percentage predicted for normal height, weight and age. Lung function decreased significantly with age and was associated with decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl concentrations. The reduction in pulmonary function correlated with elevated plasma malondialdehyde, but not with lipid hydroperoxide or protein carbonyl concentrations. Patients with severe lung dysfunction (FEV1 < 50% predicted) had higher plasma concentrations of lipid hydroperoxides than those with mild-to-moderate lung dysfunction (FEV1 > 50% pred). This study provides evidence that cystic fibrosis patients have inadequate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative lung injury contributes to the decline in pulmonary function in these patients.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Child; Child, Preschool; Cystic Fibrosis; Free Radicals; Humans; Lung; Lung Diseases; Oxidative Stress; Respiratory Function Tests; Sulfhydryl Compounds; Uric Acid; Vitamin E

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

Topics: Acetylglucosaminidase; Aging; Animals; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cell Division; Endotoxins; Epithelial Cells; Exudates and Transudates; Glutathione; Glutathione Peroxidase; Interleukin-6; Lipid Peroxides; Lung Diseases; Male; Ozone; Proteins; Rats; Rats, Inbred F344; Salmonella typhimurium; Superoxide Dismutase

Topics: Antioxidants; Ascorbic Acid; Humans; Lung Diseases

Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either an AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Desmosine; Elastin; Female; Guinea Pigs; Hydroxyproline; Lung Diseases; Lung Volume Measurements; Organ Size; Ozone; Procollagen-Proline Dioxygenase; Respiratory Function Tests; Tissue Fixation

The antiinflammatory, antioxidant activity of taurine and niacin against cyclophosphamide-induced early lung injury in rats was investigated. A single intraperitoneal injection of cyclophosphamide markedly altered the levels of several biomarkers in bronchoalveolar lavage fluid: total protein, albumin, angiotensin converting enzyme, lactate dehydrogenase, lactate, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase and lipid peroxidation product were significantly elevated. In contrast, decreased levels of total reduced glutathione (GSH) and ascorbic acid were observed. Cyclophosphamide significantly increased malondialdehyde levels in serum and lung. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione and total sulfhydryl groups. Pretreatment of rats with daily intraperitoneal injection of taurine plus niacin 7 days prior to and 2 days after cyclophosphamide insult significantly inhibited the development of lung injury, prevented the alterations in lavage fluid biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. In conclusion, our results suggest that taurine and niacin in combination is efficient in blunting cyclophosphamide-induced pulmonary damage.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acid Sequence; Animals; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cyclophosphamide; Glutathione; Lipid Peroxidation; Lung; Lung Diseases; Male; Molecular Sequence Data; Niacin; Rats; Rats, Wistar; Taurine

To determine the relative effects of cigarette smoking and mineral dust exposure on numbers and activity of circulating phagocytes, plasma nutritional antioxidant state, and pulmonary function in South African gold miners.. Pulmonary function was assessed spirometrically, whereas reactive oxidant generation by circulating phagocytes, and plasma concentrations of the nutritional antioxidative nutrients vitamin C and vitamin E and beta carotene were measured with chemiluminescence, spectrophotometry, or high performance liquid chromatography respectively.. Cigarette smoking, but not mineral dust exposure, was associated with increased numbers and pro-oxidative activity of circulating neutrophils and monocytes, decreased plasma concentrations of vitamin C, and pulmonary dysfunction.. In this study group occupational exposure to mineral dust has not been found to promote increases in the numbers or reactivity of circulating phagocytes or to be a significant cause of pulmonary dysfunction, the changes found being due primarily to cigarette smoking.

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Dust; Gold; Humans; Leukocyte Count; Lung; Lung Diseases; Male; Middle Aged; Mining; Occupational Exposure; Phagocytes; Smoking; South Africa; Spirometry; Vitamin E

An inhalation intoxication with styrene is performed on guinea pigs--600 mg.m-3, 5 hrs daily, 5 days weekly for a period of 4 weeks. The animals are put on regime lacking vitamin C. Ascorbic acid is introduced orally on 3 levels: 20 mg.kg-1 body mass (control) and with increased quantities 60 mg.kg-1 and 240 mg.kg-1 body mass. On the third day the content of ascorbic acid in some biochemical parameters of the lung is determined. Histochemical examinations of the lung tissue are made. The styrene causes decrease in the ascorbic acid content in the lung, considerable increase of the studied enzymes (lactate- and glucose-6-phosphate-dehydrogenase, alkaline and acidic phosphatase) and the concentration of the total protein in the lung. There are inflammatory, dystrophic and obturation changes. The raised intake of ascorbic acid 60 mg.kg-1 body mass doesn't effect the negative influence of styrene. The high dose (240 mg.kg-1 body mass) provokes increased activity of the examined enzymes. At inhalation with styrene this dose of ascorbic acid increases the styrene effect on the enzyme activity, especially of LDH and glucose-6-phosphate-dehydrogenase, without invigorating the pathomorphological disturbances in the lung.

Topics: Administration, Inhalation; Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Interactions; Guinea Pigs; Lung; Lung Diseases; Male; Styrene; Styrenes

Glutathione deficiency in adult mice leads to lung type 2 cell lamellar body and mitochondrial damage; as reported here, these effects are associated with marked decrease of the levels of phosphatidylcholine (the main component of lung surfactant) in the lung and the bronchoalveolar lining fluid. Severe mitochondrial damage was also found in skeletal muscle. Treatment with ascorbate (1-2 mmol per kg of body weight per day), which led to greatly increased (approximately 2-fold) levels of lung and muscle mitochondrial glutathione, prevented damage to lamellar bodies and mitochondria as well as the decline of phosphatidylcholine levels in lung and alveolar lining fluid. The findings indicate that glutathione deficiency leads to depletion of lung surfactant and that this can be prevented with ascorbate. Administration of ascorbate spares glutathione and prevents cellular damage. Lamellar body degeneration in glutathione deficiency appears to be associated with oxidative damage to the perilamellar membrane, which contains the enzymes required for phosphatidylcholine synthesis. It is notable that although severe glutathione deficiency is lethal to newborn rats, which apparently do not synthesize ascorbate, adult mice are better able to survive such a deficiency because they can synthesize ascorbate. The present studies, which suggest that high doses of ascorbate may be of therapeutic value, emphasize that ascorbate and glutathione have actions in common and that they function together in a physiologically significant antioxidant system.

Topics: Animals; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Buthionine Sulfoximine; Female; Glutathione; Lung Diseases; Methionine Sulfoximine; Mice; Microscopy, Electron; Mitochondria; Muscles; Oxidation-Reduction; Phosphatidylcholines; Pulmonary Surfactants

Topics: Ascorbic Acid; Hockey; Humans; Lung Diseases; Nitrogen Dioxide

Asbestos fibers adsorb cytochrome P-450 and P-448 proteins from rat lung micosomal fractions and liberate heme from cytochrome P-448 on prolonged incubation in vitro. further, fibers, decrease the activities of benzo(a)pyrene hydroxylase and glutathione-S-transferase in microsomal and cytosolic fractions respectively. Mineral fibers also stimulate both the enzymatic (NADPH-induced) and non-enzymatic (Fe2(+)-induced) lipid peroxidation in microsomal fractions. Preincubation of microsomal and cytosolic fractions with a physiological concentration of ascorbic acid ameliorates, to a large extent, the changes induced by asbestos fibers.

Topics: Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Ascorbic Acid; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System; Cytochromes; Female; Lipid Peroxidation; Lung; Lung Diseases; Microsomes; Rats

Topics: Animals; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Fenitrothion; Iron; L-Lactate Dehydrogenase; Lethal Dose 50; Lipid Peroxidation; Lung; Lung Diseases; Male; Mitochondria; Phospholipids; Rats; Rats, Inbred Strains

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

Reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, .OH, OX-) which are produced by stimulated alveolar macrophages (AM), neutrophils and eosinophils, play an important role in the pathogenesis of many acute and chronic lung diseases. With regard to a therapeutic application the influence of the antioxidants ascorbic acid (Vitamin C) and alpha-tocopheryl acetate (Vitamin E acetate) on the production of ROM by AM was investigated. The AM were isolated by bronchoalveolar lavage from patients with different lung disorders. The ROM were determined by means of chemiluminescence-measuring. alpha-Tocopheryl acetate solved in peanut oil causes a little increase of the yeast cell wall-induced chemiluminescence. Pure alpha-Tocopheryl acetate has no effect on the chemiluminescence. In contrast to alpha-Tocopheryl acetate the addition Vitamin C to the stimulated AM results in a strong diminution of the chemiluminescence signal. This result suggests that Vitamin C reduces the generation of ROM by AM. Therefore Vitamin C could be a suitable scavenger of radicals and oxidants in different lung diseases.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Humans; Luminescent Measurements; Lung Diseases; Macrophage Activation; Macrophages; Oxygen Consumption; Tocopherols; Vitamin E

Topics: Adenosine Triphosphate; Ascorbic Acid; Bicarbonates; Blood Transfusion; Humans; Lung Abscess; Lung Diseases; Plasma Substitutes; Potassium Chloride; Sodium; Suppuration; Thiamine Pyrophosphate

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Diet; Guinea Pigs; Liver; Lung; Lung Diseases; Organ Size; Oxygen

Topics: Adult; Ascorbic Acid; Chronic Disease; Escherichia coli Infections; Female; Humans; Infections; Lung Diseases; Male; Middle Aged; Osteomyelitis; Peritonitis; Pleural Diseases; Pneumonia; Staphylococcal Infections; Streptococcal Infections; Suppuration; Surgical Wound Infection; Tetracycline; Thiamine

Topics: Ascorbic Acid; Fetal Death; Guinea Pigs; Hypoxia; Liver Diseases; Lung Diseases; Pathology; Pharmacology; Pregnancy; Pregnancy, Animal; Research; Toxicology

Topics: Acrolein; Ascorbic Acid; Humans; Inositol; Lung Diseases; Poisoning; Vitamin A; Vitamin E; Vitamin K; Vitamins