ascorbic-acid and Liver-Diseases

Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.. To assess the benefits and harms of antioxidant supplements for patients with liver diseases.. We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to January 2011. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.. We considered for inclusion randomised trials that compared antioxidant supplements (beta-carotene, vitamin A, C, E, and selenium) versus placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease, and cirrhosis (any aetiology).. Four authors independently selected trials for inclusion and extracted data. Outcome measures were all-cause mortality, liver-related mortality, liver-related morbidity, biochemical indices at maximum follow-up in the individual trials as well as adverse events, quality-of-life measures, and cost-effectiveness. For patients with hepatitis B or C we also considered end of treatment and sustained virological response. We conducted random-effects and fixed-effect meta-analyses. Results were presented as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI).. Twenty randomised trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials), and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality (relative risk [RR] 0.84, 95% confidence interval [CI] 0.60 to 1.19, I(2) = 0%), or liver-related mortality (RR 0.89, 95% CI 0.39 to 2.05, I(2) = 37%). Stratification according to the type of liver disease did not affect noticeably the results. Antioxidant supplements significantly increased activity of gamma glutamyl transpeptidase (MD 24.21 IU/l, 95% CI 6.67 to 41.75, I(2) = 0%).. We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzyme activity.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cause of Death; Dietary Supplements; Humans; Liver Diseases; Oxidative Stress; Randomized Controlled Trials as Topic; Selenium; Vitamin A; Vitamin E

Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal.. To assess the benefits and harms of antioxidant supplements for patients with liver diseases.. We identified trials through electronic and manual searches until August 2009. We included randomized trials comparing antioxidant supplements (beta-carotene, vitamin A, C, E and selenium) vs. placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease and cirrhosis (any aetiology). Random-effects and fixed-effect meta-analyses were conducted. Results were presented as relative risks (RR), or mean difference (MD), both with 95% confidence intervals (CI).. Twenty randomized trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials) and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality [relative risk (RR) 0.84, 95% confidence interval (CI) 0.60-1.19, I(2) = 0%] or liver-related mortality (RR 0.89, 95% CI 0.39-2.05, I(2) = 37%). Stratification according to the type of liver disease assessed did not affect the conclusions. Antioxidant supplements significantly increased the activity of gamma glutamyl transpeptidase (MD 24.21 IU/L, 95% CI 6.67-41.75, I(2) = 0%).. We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzymes.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Bias; Female; Humans; Liver Diseases; Male; Middle Aged; Selenium; Vitamin A; Vitamin E

Metabolic bone disease (osteodystrophy) is an important complication of patients with chronic liver disease; its etiology is complex and multifactorial. Osteodystrophy is manifested as osteopenia/osteoporosis. Osteoporosis can predispose patients to bone fractures, increasing morbidity and mortality, especially after liver transplantation. Early evaluation, screening, and treatment of bone disorders in patients with liver disease are essential to minimize fracture risk and to improve clinical outcome and quality of life.

Topics: Ascorbic Acid; Bone and Bones; Bone Diseases, Metabolic; Calcium; Chronic Disease; Humans; Liver Diseases; Nutrition Therapy; Osteoporosis; Vitamin D; Vitamin K

Great importance has been attributed to antioxidants in the prevention and treatment of conditions associated with oxidative stress for many years. At the same time the antioxidants are free radicals themselves, and they can exert prooxidant activity depending on the concentration. They influence the cell redox homeostasis by their prooxidant and antioxidant activity as well. Drugs of chronic liver diseases should be considered, because free radicals are generated during the activity of the monooxygenase system, which affect the tissue oxidised status. Combined antioxidant treatment is more favourable compared with monotherapy, because antioxidants have scavenger-, compartment- and tissue-specificity and they regenerate each other directly, too. Beside their antioxidant property they may also directly regulate many important processes, e.g. cell cycle. We have some favourable results with regard combined antioxidant therapy of liver disease of different etiology.

Topics: Antioxidants; Ascorbic Acid; Drug Combinations; Drug Therapy, Combination; Free Radical Scavengers; Free Radicals; Humans; Liver; Liver Diseases; Mixed Function Oxygenases; Organ Specificity; Oxidation-Reduction; Oxidative Stress; Pyridoxine; Pyrrolidonecarboxylic Acid; Silymarin; Vitamin A; Vitamin E

Oxidation is a biochemical process of loss of electrons associated with another of reception called reduction. This process is capital for life, because it takes part in the production of cellular energy. Oxidative stress appears when oxidation is excessive. This reality is complex in all biological levels, and cannot be measured or defined by a single parameter. A great number of diseases have been related to oxidative stress and generation of free radicals. For this reason, antioxidant therapies and diets (such as mediterranean diet) rich or enriched with antioxidants seem to prevent or at least to attenuate the organic deterioration originated by an excessive oxidative stress.

Topics: Acute Kidney Injury; Aged; Aging; Antioxidants; Arteriosclerosis; Ascorbic Acid; beta Carotene; Cataract; Diabetes Mellitus; Diet; Humans; Hypertension; Liver Diseases; Neoplasms; Oxidation-Reduction; Oxidative Stress; Primary Prevention; Risk Factors; Selenium; Vitamin E

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.

Topics: Aging; Antioxidants; Ascorbic Acid; Fatty Acids, Unsaturated; Free Radicals; Glutathione; Heart Diseases; Humans; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Membranes; Neoplasms; Vitamin E

Recent investigations have begun to define more clearly the cellular and molecular roles of oxidant stress in mediating the liver injury and fibrosis of metal storage diseases. Because of a variety of perturbations in antioxidant homeostasis in iron and copper overload, restoring the antioxidant balance to normal, or even exceeding normal levels of selected antioxidants, may provide additional protection against liver injury and prevent the progression to fibrosis and cirrhosis. Inasmuch as GSH levels appear to be elevated in livers of experimentally iron-overloaded animals, attempts to increase this antioxidant should perhaps be limited to copper overload conditions in which hepatic GSH is low. Vitamin C (ascorbate) supplementation should probably be avoided in all metal overload states because of its potentiation of radical generation by transition metals. The safety of beta-carotene in alcoholic liver disease has been questioned. Therefore, until more is known about its toxicity in metal overload, beta-carotene may not be an ideal antioxidant for clinical trials. Vitamin E and related compounds, therefore, appear to be the most reasonable antioxidants to test in metal overload states at this time. In the near future, the results of controlled clinical trials of the use of antioxidants in these and other liver disorders will hopefully provide clearer guidelines for their safety and possible use.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chemical and Drug Induced Liver Injury; Copper; Glutathione; Iron; Liver Cirrhosis, Experimental; Liver Diseases; Liver Diseases, Alcoholic; Metals; Oxidative Stress; Vitamin E

Topics: Adolescent; Arrhythmias, Cardiac; Ascorbic Acid; Blood Transfusion; Child; Cholelithiasis; Deferoxamine; Endocrine System Diseases; Female; Folic Acid; Growth Disorders; Heart Failure; Hematopoiesis; Humans; Iron; Leg Ulcer; Liver Diseases; Male; Pericarditis; Splenectomy; Thalassemia; Vitamin E

Topics: Adolescent; Adult; Ascorbic Acid; Blood Transfusion; Cardiomyopathies; Deferoxamine; Dose-Response Relationship, Drug; Ferritins; Growth Disorders; Heart Diseases; Hemosiderosis; Humans; Iron; Iron Chelating Agents; Liver; Liver Diseases; Pancreatic Diseases; Parathyroid Diseases; Pituitary Diseases; Thyroid Function Tests

Topics: Ascorbic Acid; Celiac Disease; Citrates; Colitis, Ulcerative; Crohn Disease; Dietary Fats; Gastrointestinal Diseases; Humans; Hyperparathyroidism; Ileostomy; Intestine, Small; Liver Diseases; Malabsorption Syndromes; Oxalates; Solubility; Urinary Calculi

Topics: Ascorbic Acid; Calcium; Chronic Disease; Clinical Trials as Topic; Female; Humans; Liver Diseases; Magnesium; Male; Methenolone; Methionine; Vitamin A; Vitamin B Complex; Vitamins

Topics: Adult; Aged; Ascorbic Acid; Blood Proteins; Clinical Trials as Topic; Folic Acid; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Middle Aged; Nicotinic Acids; Vitamin B 12

Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of sepsis. In excess, oxidative stress is not deemed an unbalanced biochemical reaction in the critically ill rats, but it is a key pathological factor in driving systemic inflammatory response that can result in multiple organ failure in sepsis. Thus, we aimed to explore whether antioxidant nutrients could reduce or delay the oxidative stress condition of sepsis rats, and then play a prospective role in the oxidative stress condition of critical disease. In this investigation, the ability of exogenous and endogenous antioxidant nutrients (ascorbate, taurine and glutathione) to prevent sepsis-induced changes in liver injury was examined using a rat model of sepsis induced by cecal ligation and puncture (CLP), and the underlying mechanisms were also investigated. The effects of three antioxidants on sepsis were assessed based on biochemical assays in combination with an NMR-based metabolomics approach and correlation network analysis. Our results suggested that ascorbate, taurine and glutathione had broadly similar protective effects on reducing oxidative stress. Compared with CLP rats, antioxidant-treated rats exhibited alleviated (P<.05) organ dysfunction and improved liver pathology. Moreover, taurine showed a better efficacy compared with ascorbate and glutathione, evidenced by significantly reversed metabolomics profiles toward normal state. Under conditions of sepsis, antioxidants suppressed inflammatory responses by restraining key signaling pathways, including the redox-sensitive transcription factor pathways of NF-κB and MAPK. Collectively, our findings suggested that antioxidant nutrients exerted beneficial effects on septic rats via protecting mitochondrial.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Glutathione; Liver Diseases; Magnetic Resonance Spectroscopy; Male; Metabolome; Metabolomics; Nutrients; Oxidative Stress; Rats; Sepsis; Taurine

Liver ischemia and reperfusion injury (IRI) is a major problem associated with liver surgery. This study is aimed to compare the preventive effect of an antioxidative nutrient-rich enteral diet (Ao diet) with an ordinal enteral diet (control diet) against liver IRI.. The Ao diet was an ordinary diet comprising polyphenols (catechin and proanthocyanidin) and enhanced levels of vitamins C and E. Male C57BL/6 mice were fed the Ao or control diet for 7 days before ischemic insult for 60 minutes, followed by reperfusion for 6 hours. The levels of inflammatory cytokines, chemokines, and antioxidant enzymes and oxidative stress were evaluated.. After 7 days of pretreatment with the Ao diet, the serum levels of vitamins C and E in mice were markedly elevated. The levels of serum aspartate aminotransferase and alanine aminotransferase, as well as the scores of liver necrosis caused by ischemia and reperfusion, were significantly lower in the Ao diet group than in the control diet group. The gene expression levels of inflammatory cytokines and chemokines, such as interleukin-6 and CXCL1, were significantly lower in the Ao diet group. In the liver, the levels of antioxidant enzymes superoxide dismutase 1 (SOD1) and SOD2 were significantly higher and the malondialdehyde levels were significantly lower in the Ao diet group. Cell adhesion molecule expression was significantly lower, and neutrophil and macrophage infiltration was less in the Ao diet group.. Antioxidative nutrient supplementation to an ordinary enteral diet may mitigate liver IRI by causing an antioxidant effect and suppressing inflammation.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Catechin; Diet; Digestive System Surgical Procedures; Enteral Nutrition; Food, Fortified; Ischemia; Liver; Liver Diseases; Male; Malondialdehyde; Mice, Inbred C57BL; Oxidative Stress; Plant Extracts; Proanthocyanidins; Reperfusion Injury; Superoxide Dismutase; Vitamin E

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

Vitamin C, an excellent reducing agent, aids in increasing absorbable ferrous iron in iron deficiency anemia. As an efficient antioxidant, it is still unknown whether vitamin C exerts protective effects against liver damage caused by iron excess and whether mitochondria are the target effectors of the above effects. In this study, 48 mice were randomly divided into a control group, iron-overload group, TAU-treated + iron-overload group and vitamin C-treated + iron-overload group with 12 mice per group. The mice were fed 4 months on pellet diets supplemented with iron in the form of ferrocene. The iron ratio in the diet was maintained at 0.2% (w/w) for 90 days and then 0.4% (w/w) for the remaining 30 days. Furthermore, 2 g kg-1 vitamin C and 20 mg kg-1 TAU were administered daily by oral gavage prior to iron-overload administration at 6 weeks and throughout the course of the experiments. We investigated the protective effects of vitamin C against liver damage by assessing the liver weight to body weight ratio (LW/BW), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and histological changes. In addition, enzymatic and non-enzymatic antioxidants, reactive oxygen species (ROS) generation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were evaluated to clarify the antioxidant effects of vitamin C. We found that vitamin C significantly attenuated impaired liver function in mice induced by iron overload via antioxidation, whereas no significant effect on iron uptake was observed. Vitamin C targeted the mitochondria, preventing mitochondrial swelling, MMP dissipation, and ROS burst, thus inhibiting hepatic apoptosis. Collectively, our results suggest that vitamin C acts as a "double agent" in iron supplementation therapy for iron deficiency anemia, boosting iron absorption for preventing iron deficiency and preventing liver damage due to excessive iron intake during treatment.

Topics: Alanine Transaminase; Anemia, Iron-Deficiency; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Dietary Supplements; Ferrous Compounds; Glutathione Peroxidase; Humans; Iron; Iron Overload; Liver; Liver Diseases; Male; Malondialdehyde; Membrane Potential, Mitochondrial; Metallocenes; Mice; Oxidative Stress; Reactive Oxygen Species

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

The present study aims to determine the potential of melatonin supplementation in ameliorating tissue oxidative stress, elevated serum corticosterone and hepatic and renal dysfunction.. Adult Wistar rats, either ovariectomized or sham-operated, served as experimental or control groups, respectively. Rats received either melatonin, estrogen, progesterone or a combination of melatonin and estrogen for a period of 15 days. Tissue oxidative stress, serum markers of hepatic and renal dysfunction and serum corticosterone level formed the parameters of assay in all groups at the end of the treatment schedule.. Ovariectomized rats showed significant increases in levels of tissue lipid peroxidation, serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, acid phosphatase and corticosterone and significant decrement in enzymatic and non-enzymatic antioxidant status. All parameters showed maximal reversal to control levels on supplementation with high-dose melatonin or estrogen + melatonin treatment.. Melatonin supplementation proved better than estrogen replacement therapy, with the higher dose being more effective in preventing ovariectomy-induced increases in oxidative stress and serum levels of marker parameters of hepatic and renal dysfunction and corticosterone titer. Overall, melatonin supplementation therapy qualifies as a more potent and safe alternative to estrogen replacement therapy in alleviating postmenopausal increases in oxidative stress and hepatic and renal dysfunction.

Topics: Animals; Ascorbic Acid; Catalase; Corticosterone; Estrogen Replacement Therapy; Estrogens; Female; Glutathione; Glutathione Peroxidase; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Melatonin; Ovariectomy; Oxidative Stress; Progesterone; Rats; Rats, Wistar; Superoxide Dismutase

The Pringle maneuver is a surgical procedure to minimize hemorrhage during hepatectomy, which however, can induce production of reactive oxygen species causing remote organ injury. We sought to study the impact of the Pringle maneuver on cardiac function as well as the protective effects of L-ascorbic acid and α-tocopherol pretreatments.. Rats were divided into four study groups: L-ascorbic acid (60 mg/kg/d) or α-tocopherol (200 mg/kg/d), and surgical interventions (Sham-operated or liver ischemia-reperfusion [I/R]). Liver ischemia was performed by clamping the hepatic artery and portal vein for 30 minutes, followed by reperfusion by releasing the clamps for 2 hours. Cardiac function was evaluated by a high-fidelity pressure-volume catheter positioned in the left ventricle. Myocardial injury was assessed through plasma creatine kinase-MB (CKMB) and troponin I (cTnI). Cardiac lipid peroxidation and systemic hydroxyl radical levels were assessed by cardiac tissue malondialdehyde and plasma methylguanidine, respectively.. Cardiac function was significantly depressed in the I/R group, where plasma CKMB and cTnI were markedly increased (P < .05). L-ascorbic acid and α-tocopherol pretreatments improved cardiac function and significantly reduced cardiac injury (P < .05). L-ascorbic acid pretreatment demonstrated better heart protection than α-tocopherol, in terms of cTnI and CKMB (P < .05), but no significant difference in terms of cardiac functional improvement.. L-ascorbic acid and α-tocopherol pretreatment 3 days prior to the Pringle maneuver attenuated myocardial injury and protected cardiac function by scavenging hydroxyl radical and reducing lipid peroxidation. L-ascorbic acid demonstrated better protection than α-tocopherol.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cardiac Catheterization; Creatine Kinase, MB Form; Disease Models, Animal; Heart Diseases; Hepatectomy; Hydroxyl Radical; Lipid Peroxidation; Liver Diseases; Malondialdehyde; Methylguanidine; Myocardial Contraction; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors; Troponin I; Ventricular Function, Left; Ventricular Pressure

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Topics: Animals; Ascorbic Acid; Autoanalysis; Biomarkers; Clonixin; Dexamethasone; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Enrofloxacin; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Heart Diseases; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Shock, Septic; Superoxide Dismutase; Time Factors

The aim of this study was to examine whether an antioxidant combination of vitamin C, vitamin E, and sodium selenate (Se) has an effect on the liver of diabetic rats. Vitamin C, vitamin E, and Se were administered for 30 days to streptozotocin (STZ)-induced diabetic and control groups. In the STZ diabetic group, blood glucose levels, liver lipid peroxidation (LPO), and nonenzymatic glycosylation (NEG) levels increased, but blood and liver glutathione levels decreased. On the other hand, combined antioxidant treatment reversed these effects. In the diabetic group, some degenerative changes were observed by light and electron microscopic examinations, but the degenerative changes decreased in the diabetic group given antioxidant combination. Proliferating cell nuclear antigen (PCNA) immunohistochemistry showed that the number of proliferative hepatocytes increased significantly with antioxidant treatment. It was concluded that combined treatment with vitamin C, vitamin E, and Se has a curative effect against the hepatotoxicity produced by STZ-induced diabetes.

Topics: Animals; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Female; Liver; Liver Diseases; Rats; Selenic Acid; Selenium Compounds; Vitamin E

Pyrethroid pesticides were used preferably over organochlorines and organophosphates due to their high effectiveness, low toxicity to non-target organisms and easy biodegrability. It has widespread applications in agriculture through the world and in Tunisia. The present study investigates lambda-cyhalothrin (LTC) effects on biochemical parameters, hepatotoxicity and their attenuation by vitamin C. Male Wistar rats were randomly divided into three groups of seven each: a control group (C) and two treated groups during 3 weeks with LTC administrated either alone in drinking water for LTC group or coadministred with vitamin C for LTC+vit C group. Lactate deshydrogenase (LDH) activity was significantly increased in liver (+51%, p<0.001) and in plasma (+40%, p<0.001) compared to those of control group. A significant increase of malondialdehyde (MDA) levels in liver (+53%; p<0.001) associated with a decrease in antioxidants enzyme activities and reduced glutathione (GSH) content was observed in LTC group compared to controls. The administration of vitamin C to LTC+vit C group improved all parameters studied. We conclude that LTC induces oxidative stress and modifies biochemical parameters and histological aspects of liver. Administration of vitamin C alleviates the toxicity induced by this synthetic pyrethroid insecticide.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Catalase; Chemical and Drug Induced Liver Injury; Glutathione; Insecticides; L-Lactate Dehydrogenase; Liver Diseases; Male; Malondialdehyde; Nitriles; Pyrethrins; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamins

A hundred and fifty-two patients cholelithiasis were examined. Among them, 69 and 83 patients were operated on for acute destructive and chronic cholecystitis, respectively. In destructive cholecystitis, there is a high lipid oxidation rate accompanied by the elevated levels of nonenzymatic antioxidant ceruloplasmin. The low activity of catalase and ceruloplasmin and the decreased content of ascorbic acid suggest the depletion of antioxidative defense in patients with cholelithiasis with significant liver disease. The magnitude of changes in the activity of antioxidative enzymes and the level of the nonenzymatic antioxidant ascorbic acid depend on the state of the liver.

Topics: Antioxidants; Ascorbic Acid; Catalase; Ceruloplasmin; Cholecystitis, Acute; Cholelithiasis; Chronic Disease; Female; Humans; Liver Diseases; Male; Oxidation-Reduction

Our experiments showed that 18 h restraint stress could induce serious liver damage, with an increase in plasma alanine aminotransferase (ALT) level (107.68 +/- 3.19 U/L vs 18.08 +/- 1.46 U/L). Meanwhile, we observed increased malondialdehyde (MDA) levels and lowered oxygen radical absorbance capacity (ORAC) values in plasma and liver of restraint mice compared with starved mice. Bilberry extract (containing 42.04% anthocyanins) was oral administrated to mice at 50, 100, and 200 mg/(kg x day) for five days, which remarkably decreased plasma ALT level to 17.23 +/- 2.49 U/L at the dose of 200 mg/(kg x day) and thus alleviated stress-induced liver damage. In addition, bilberry extracts increased glutathione (GSH) and vitamin C levels and significantly decreased MDA and nitric oxide (NO) levels in the liver tissues. These results suggest that bilberry extract plays an important role in protecting against restraint stress-induced liver damage by both scavenging free radicals activity and lipid peroxidation inhibitory effect. This study showed the beneficial health effects of bilberry extract through its antioxidative action.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Glutathione; Liver Diseases; Male; Malondialdehyde; Mice; Nitric Oxide; Plant Extracts; Restraint, Physical; Stress, Physiological; Vaccinium myrtillus

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

The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and L-arginine on hepatic damage induced by caerulein-pancreatitis.. The liver specimens of all groups showed histopathological alterations such as hepatocyte necrosis, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration. TEM studies revealed vacuole formation, mitochondrial degeneration, lysosome accumulation and necrosis. The mean histopathological score of the caerulein group was significantly different from that of each treatment group.. L-Arginine and antioxidant administration be important for reducing hepatic damage induced by AP. Improvement of hepatic damage, in turn, might be beneficial for the prognosis of AP.

Topics: Acetylcysteine; Acute Disease; Animals; Antioxidants; Arginine; Ascorbic Acid; Ceruletide; Female; Liver Diseases; Melatonin; Pancreatitis; Pentoxifylline; Rats; Rats, Wistar; Statistics, Nonparametric

Cadmium is an environmental toxic metal implicated in human diseases. In the present study, the effect of diphenyl diselenide, (PhSe)(2), on sub-chronic exposure with cadmium chloride (CdCl(2)) was investigated in rats. Male adult Swiss albino rats received CdCl(2) (10 micromol/kg, orally) and (PhSe)(2) (5 micromol/kg, orally) for a period of 30 days. A number of parameters were examined as indicators of toxicity, including hepatic and renal damage, glucose and glycogen levels and markers of oxidative stress. Cadmium content, liver histology, delta-aminolevulinate dehydratase (delta-ALA-D) activity, metallothionein (MT) levels were also evaluated. Cadmium content determined in the tissue of rats exposed to CdCl(2) provides evidence that the liver is the major cadmium target where (PhSe)(2) acts. The concentration of cadmium in liver was about three fold higher than that in kidney, and (PhSe)(2) reduced about six fold the levels of this metal in liver of rats exposed. Rats exposed to CdCl(2) showed histological alterations abolished by (PhSe)(2) administration. (PhSe)(2) administration ameliorated plasma malondialdehyde (MDA) levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) activities increased by CdCl(2) exposure. Urea and bilirubin levels increased by CdCl(2) exposure were also reduced by (PhSe)(2). In conclusion, this study demonstrated that co-treatment with (PhSe)(2) ameliorated hepatotoxicity and cellular damage in rat liver after sub-chronic exposure with CdCl(2). The proposed mechanisms by which (PhSe)(2) acts in this experimental protocol are its antioxidant properties and its capacity to form a complex with cadmium.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Benzene Derivatives; Bilirubin; Blood Glucose; Cadmium; Cadmium Chloride; Chemical and Drug Induced Liver Injury; gamma-Glutamyltransferase; Glycogen; Kidney; L-Lactate Dehydrogenase; Liver; Liver Diseases; Male; Malondialdehyde; Organoselenium Compounds; Oxidative Stress; Porphobilinogen Synthase; Rats; Rats, Wistar; Sulfhydryl Compounds

D-Galactosamine (D-GaIN) is a highly selective hepatotoxin that causes liver injury similar to human viral hepatitis via depletion of uridine nucleotides, which subsequently diminishes synthesis of RNA and proteins. The aim of this study was to investigate the role of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol on D-GaIN-induced liver injury of rats by morphological and immunohistochemical means. In this study, Sprague-Dawley female rats were divided into four groups. Group I consists of rats injected physiologic saline solution intraperitoneally. Group II consists of rats given selenium (0.2 mg/kg per day), ascorbic acid (100 mg/kg per day), beta-carotene (15 mg/kg per day), and alpha-tocopherol (100 mg/kg per day) for 3 days via gavage method. Group III consists of the single dose of D-GaIN (500 mg/kg)-injected animals. Group IV are the D-GaIN-injected animals given the same antioxidant combination. In situ terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay was applied to determine apoptosis for paraffin sections of the liver samples. Moreover, caspase-3 and proliferating cell nuclear antigen antibody were applied for paraffin sections. In the group given D-GaIN, apoptotic cells with TUNEL assays and caspase-3 activity, which are liver injury markers induced by D-GaIN, the hepatocyte proliferation with cell proliferation assay increased. However, selenium and other three antioxidants combination clearly suppressed an increase in apoptotic cells with TUNEL assay and caspase-3 activity. In addition, it suppressed D-GaIN-induced cell proliferation in the liver. As a result, these results indicate that selenium and three naturally occurring antioxidants shows a protective effect against liver injury induced by D-GaIN. These results suggest that supplementation with the combination of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol may help prevent the development of liver injury.

Topics: alpha-Tocopherol; Animals; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Caspase 3; Cell Proliferation; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Female; Galactosamine; Immunohistochemistry; In Situ Nick-End Labeling; Liver; Liver Diseases; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Selenium

Cadmium (Cd), a widely distributed toxic trace metal, has been shown to accumulate in liver after long- and short-term exposure. Cd (2 mg/kg/day CdCl2) was intraperitoneally given to rats for eight days. Vitamin C (250 mg/kg/day) + vitamin E (250 mg/kg/day) + sodium selenate (0.25 mg/kg/day) were given to rats by oral means. The animals were treated by anti-oxidants one hour prior to treatment with Cd every day. The degenerative changes were observed in the groups given only Cd and anti-oxidants + Cd. Metallothionein (MT) immunoreactivity increased in cytoplasm of hepatocytes of the rats given Cd when compared with controls. In a number of cells with Cd and anti-oxidants treatment, immunoreactivity increase was more than in the group given Cd only and nuclear MT expression was also detected. Cell proliferation was assessed with proliferating cell nuclear antigen (PCNA) immunohistochemistry. PCNA expressions increased in all groups more than in the controls. Anti-oxidants treatment increased cell proliferation. In the animals administered with Cd, an increase in serum aspartate (AST) and alanine (ALT) aminotransferases, liver glutathione (GSH) and lipid peroxidation (LPO) levels were observed. On the other hand, in the rats treated with anti-oxidants and Cd, serum AST and ALT, liver glutathione and LPO levels decreased. As a result, these results suggest that combined anti-oxidants treatment might be useful in protection of liver against Cd toxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Cadmium; Cadmium Poisoning; Chemical and Drug Induced Liver Injury; Hepatocytes; Lipid Peroxidation; Liver Diseases; Male; Metallothionein; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Selenic Acid; Selenium Compounds; Vitamin E

Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce hepatocyte apoptosis and liver injury; however, the mechanisms have not been fully elucidated. In the present study, we investigated whether MC-LR stimulated ROS generation in the liver of mice and the role of ROS in the pathogenesis of MC-LR-induced liver injury in vivo. MC-LR treatment (60 microg/kg of body weight) for 12h prompted large amount of ROS generation in mice liver, upregulated the expression of Bax and Bid, caused the mitochondrial membrane potential (MMP) loss and hepatocyte apoptosis as well as liver injury. While pretreatment with antioxidants, oral administration of vitamin C (250mg/kg of body weight, dissolved in double distill water) and vitamin E (200mg/kg of body weight, dissolved in corn oil) per day for 3 days continually, significantly reduced the generation of ROS and effectively inhibited the MC-LR-induced hepatocyte apoptosis and liver injury, suggesting that ROS played a critical role in MC-LR-induced hepatocyte apoptosis and liver injury. The protective effect of vitamin C and E also suggested the potential interest in the clinical treatment of MC-LR-induced liver injury and hepatotoxicity.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Aspartate Aminotransferases; bcl-2-Associated X Protein; BH3 Interacting Domain Death Agonist Protein; Chemical and Drug Induced Liver Injury; Hepatocytes; Histocytochemistry; Liver Diseases; Male; Malondialdehyde; Marine Toxins; Membrane Potential, Mitochondrial; Mice; Mice, Inbred ICR; Microcystins; Random Allocation; Reactive Oxygen Species; Rhodamines; Vitamin E

High-fat diets and oxidative damage may contribute to the development of type 2 diabetes. Hypolipidaemic drugs and antioxidants were supposed to prevent the development of the disease. In this study, we investigated preventive effects of fenofibrate (200 mg kg(-1)), vitamin C (30 mg kg(-1)), combination of both in mice induced by streptozotocin (35 mg kg(-1)) and soluble lard (15 ml kg(-1)). The results showed the mice demonstrated hyperglycaemia and hypercholesterolaemia, visceral fat accumulation, and a slight increase in liver glycogen/triglyceride and oxidative stress within 60 days of treatment. Fenofibrate enhanced insulin sensitivity, improved glycaemic control, lowered serum triglycerides, reduced body and visceral fat weights, and decreased liver glycogen/lipid levels but showed hepatotoxicity in the mice. Vitamin C neither itself prevented nor enhanced preventive effects of fenofibrate on glucose and lipid metabolism but partly attenuated the hepatotoxicity of fenofibrate. These results suggest that fenofibrate inhibit development of type 2 diabetes induced by high-fat diets and oxidative stress. However, here, vitamin C just can serve as an adjunct to fenofibrate therapy against its hepatotoxicity. In the future study, we should investigate if higher dosage of vitamin C or other antioxidants would enhance preventive effects of fenofibrate in type 2 diabetes.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Chemical and Drug Induced Liver Injury; Cholesterol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Drug Therapy, Combination; Fenofibrate; Glycogen; Hypercholesterolemia; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Intra-Abdominal Fat; Liver; Liver Diseases; Male; Matrix Metalloproteinase 9; Mice; Oxidative Stress; Streptozocin; Triglycerides

To investigate the effect of ascorbic acid [vitamin C (VC)] on liver damage parameters in the lead-exposed mice, when given in combination with thiamine [vitamin B1 (VB(1))] at different concentrations.. Sixty-six male mice were randomly assigned into 11 groups (n = 6). Mice in Group I were supplied with only the tap water as the drinking water; mice in Group II were provided with a tap water containing 0.2% lead acetate; mice in Group III-XI were given different dose of VC (140, 420, 1260 mg kg(-1) bw) and VB(1) (10, 30, 90 mg kg(-1) bw) according to 3 x 3 factorial design by oral gavages, along with ingestion of 0.2% lead acetate. After 42 test days, DNA damage of liver cells was assessed using single-cell gel electrophoresis. The apoptosis rate of liver cells was determined by flow cytometry. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood and the level of reduced glutathione (GSH) in liver cells were measured based on individual biochemical reactions.. Compared with the Group I, sub-chronic lead ingestion (Group II) resulted in a significant decrease of Hb, GSH-P(X), SOD in blood and GSH level in liver cells; lead exposure induced also a significant increase in DNA damage and apoptosis of liver cells (P < 0.05). Supplementation with VC and VB(1), however, reversed these effects. The best effective combination was VC (420 mg kg(-1) bw) and VB(1) (10 mg kg(-1) bw), followed by the combination of VC (420 mg kg(-1) bw) and VB(1) (30 mg kg(-1) bw). But no reversion was shown in the combination of the highest combination of VC (1260 mg kg(-1)) and VB(1) (90 mg kg(-1)).. These findings strongly indicated that combination of VC and VB(1) can lessen the damage to liver cells from oxidative stress induce by lead, but the antioxidant effects are dependent on their concentrations.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Dietary Supplements; DNA Damage; Environmental Pollutants; Lead; Liver; Liver Diseases; Male; Mice; Oxidative Stress; Thiamine; Vitamin B Complex; Vitamins

Radical scavenging activity of ethanolic extract of Trianthema triquetra root was investigated against CCl4 in rats. The rats were treated with T. triquetra (100 mg, 200 mg/kg b.w.) for a period of 7 days. Antihepatotoxic effect was studied by assaying the activities of thiobarbituric acid (TBARS), reduced glutathione (GSH), glutathione peroxidase (GPx),catalase (CAT), super oxide dismutase (SOD) and vitamin C (Vit. C). Lipid peroxidation is evidenced by an increase in the value of TBARS and also a distinct diminution in the level of GSH, Vit. C at 200 mg/kg b.w. The activity of antioxidant enzymes, such as GPx, CAT SOD and Vit. E is significantly recovered towards an almost normal level in animals coadministrated with T. triquetra. The maximum protection against CCl4 induced hepatic injury was afforded by the dose of 200 mg/kg b.w. of Trianthema triquetra.

Topics: Aizoaceae; Animals; Ascorbic Acid; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Ethanol; Free Radical Scavengers; Glutathione; Glutathione Reductase; Liver Diseases; Male; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.

Topics: Aflatoxin B1; Animals; Antioxidants; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Transferase; Lipid Peroxidation; Liver; Liver Diseases; Male; Oxidoreductases; Pentacyclic Triterpenes; Rats; Rats, Wistar; Silymarin; Triterpenes; Vitamin E

To observe the protective effects of tanshinones (tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone) against liver injury in mice loaded with restraint stress.. The liver injury model was established under 12 h restraint stress in mice 5 days after tanshinones treatment. The hepatoprotective effects were evaluated by assessing alanine aminotransferase (ALT) levels in plasma. The contents of vitamin C, GSH and malondialdehyde (MDA) in liver were performed by HPLC and TBARS methods, respectively. Oxygen radical absorbance capacity (ORAC) assay was used to measure the antioxidant capacity.. Tanshinones decreased ALT and MDA levels, and increased ORAC, vitamin C and GSH levels in liver tissues as compared with restraint stress control. Tanshinones also significantly inhibited oxidation in vitro. Among four tanshinones, dihydrotanshinone was more effective than others both in vivo and in vitro test.. Tanshinones possesses potent antioxidant activity in vitro and in vivo, and protected against liver injury induced by restraint stress. The active mechanisms may be related to their antioxidant capability.

Topics: Abietanes; Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Drugs, Chinese Herbal; Glutathione; Liver; Liver Diseases; Male; Malondialdehyde; Mice; Phenanthrenes; Plants, Medicinal; Protective Agents; Reactive Oxygen Species; Restraint, Physical; Salvia miltiorrhiza; Stress, Physiological

The oxidant properties of iron-overload and simultaneous ethanol consumption have received much interest, due to evidence reporting from hereditary hemochromatosis (HC). The full form of this disease is often associated with chronic alcoholism. An additive effect of toxicity of iron and ethanol was assumed. In this study, we examined nutritively iron-loaded Wistar rats (n = 59) (TMH-Ferrocene) additionally fed with ethanol up to 8% in drinking water for 36 wk.. By reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole and retinol in serum and liver homogenates as well as transaminases in the serum. Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron concentration in the liver was measured with the Bathophenanthrolin-method. Liver histology was performed to investigate the iron deposits and the organ damage (H.E., Azan and Berlin-blue-stainings).. 1. Vitamin C: A linear decrease of the concentration of vitamin C in serum and liver was found independent of alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin A: Elevated levels in serum but strongly decreasing levels in liver could be measured. 4.. All iron-fed animals showed massive deposits of iron in the liver. Iron diet caused liver cirrhosis, while an additional administration of ethanol could prevent this. 5. Lipid peroxidation increased in animals fed ethanol and iron, but was significantly lower in animals only receiving an iron diet.. Evidence indicates that the additional exposition to ethanol in iron-loaded animals could modulate the organ damage and oxidative stress. The biochemical findings are positively correlated to the histology.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Chromatography, High Pressure Liquid; Ethanol; Female; Iron; Iron Overload; Lipid Peroxidation; Liver; Liver Diseases; Rats; Rats, Wistar; Tocopherols; Vitamin A

We examined the effect of melatonin in prooxidant and antioxidant state in the liver of C57BL/6J mice fed on a high cholesterol (HC) diet. Mice were fed with normal mice chow containing 1.5% cholesterol and 0.5% cholic acid for 4 months without and with melatonin (10 mg/L in drinking water) treatment. HC diet was observed to increase malondialdehyde (MDA) and diene conjugate (DC) levels in the liver. This diet lowered glutathione (GSH), alpha-tocopherol, and total ascorbic acid levels as well as glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in the liver, but hepatic superoxide dismutase (SOD) activity remained unchanged. Although melatonin treatment did not affect these parameters in mice fed a normal diet, it reduced hepatic MDA and DC levels in mice fed an HC diet. Hepatic alpha-tocopherol and ascorbic acid levels increased, but hepatic GSH levels remained unchanged in the melatonin-treated HC group as compared to the HC group. Melatonin treatment was found to increase liver GSH-Px and GST activities in mice fed an HC diet. However, SOD activity did not alter in the liver of hypercholesterolemic mice following melatonin treatment. In addition, the histopathological lesions observed in the cholesterol-plus-melatonin group were less severe than those seen in the cholesterol group. According to these observations, we can say that melatonin treatment has an ameliorating effect on the disturbances in prooxidant and antioxidant balance and histopathological lesions in the liver of mice following cholesterol feeding.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Cholesterol, Dietary; Diet; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Liver; Liver Diseases; Malondialdehyde; Melatonin; Mice; Mice, Inbred C57BL; Oxidants; Superoxide Dismutase

Normal human hepatocytes are an ideal source of liver-targeted cell therapies, such as hepatocyte transplantation and bioartificial livers, but availability of human donor livers for liver cell isolation is severely limited. To effectively utilize scarce donor organs for cell therapies, it is of extreme importance to establish an efficient isolation technique and an effective cold preservation solution for transportation of isolated cells. A lateral segment of the liver was surgically resected from pigs weighing 10 kg and a four-step collagenase and dispase digestion was conducted. Isolated hepatocytes were subjected to 8-h cold storage on ice. The following preservation solutions were tested: 1) University of Wisconsin (UW) solution, 2) UW with 100 microg/ml of ascorbic acid-2 glucoside (AA2G), 3) 100% fetal bovine serum (FBS), and 4) Dulbecco's modified Eagle's medium (DMEM) supplemented with 100% FBS. The mean viability of porcine hepatocytes was 95.5 +/- 2.5% when isolated in three independent experiments. Viability, plating efficiency, membrane stability, and ammonia metabolic capacity of cold-preserved hepatocytes were significantly better maintained by the use of UW solution. When AA2G (100 microg/ml) was combined with UW solution, such parameters were further improved. It was explained by inhibition of caspase-3 activation and retention of ATP at high levels of hepatocytes preserved with UW solution containing AA2G. The present work demonstrates that a combination of UW solution with AA2G (100 microg/ml) would be a useful cold preservation means for the development of cell therapies.

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Ammonia; Animals; Apoptosis; Ascorbic Acid; Caspase 3; Caspase Inhibitors; Caspases; Cell Culture Techniques; Cell Membrane; Cell Separation; Cell Survival; Cell Transplantation; Cells, Cultured; Cryopreservation; Cryoprotective Agents; Glutathione; Hepatocytes; Insulin; Liver Diseases; Liver Transplantation; Male; Organ Preservation Solutions; Raffinose; Sus scrofa; Transplantation, Heterologous

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GS

Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Biological Availability; Cardiovascular Diseases; Dose-Response Relationship, Drug; Flow Cytometry; Free Radical Scavengers; Free Radicals; Humans; Keratinocytes; Kidney Diseases; Liver Diseases; Neoplasms; Plant Extracts; Proanthocyanidins; Seeds; Vitamin E

We have applied our method for the simultaneous detection of plasma ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto, Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in these patients. The average ubiquinone-10 percentages (+/- S.D.) in total ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/- 10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant increase in ubiquinone-10 percentage in patient groups in comparison to normal subjects. These results and a significant decrease in the plasma ascorbate level in patient groups indicate that oxidative stress is evident after the onset of hepatitis and the subsequent cirrhosis and liver cancer.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Cholesterol; Cholesterol Esters; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Ubiquinone; Vitamin E

Topics: Acid Phosphatase; Alanine Transaminase; Animals; Antibiotics, Antineoplastic; Ascorbic Acid; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Confidence Intervals; Daunorubicin; Liver Diseases; Male; Rats; Rats, Wistar; Vitamin E

Vicolides A,B, C and D, the sesquiterpene lactones isolated from V. indica exhibited antiinflammatory activity against cotton pellet granuloma in rats at dose level of 10 mg/kg body weight, sc. Highly significant activity was observed with vicolides C and D. They reduced the protein content, acid and alkaline phosphatase, glutamate-pyruvate transaminase and glutamate oxaloacetate transaminase activities in liver and serum. Significant reduction in ascorbic acid content in adrenals was also observed in treated animals. The highly significant antiinflammatory activity of vicolides C and D can be attributed to their chemical structures. Vicolide D has an epoxy angeloyl group while vicolide C has 3,4 epoxy group and an ester moiety in the molecule. Vicolide D possesses antipyretic activity at 250 mg/kg body weight, po dose. It may be due to the presence of epoxy angeloyl group in the molecule.

Topics: Adrenal Glands; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Enzymes; Granuloma; Lactones; Liver; Liver Diseases; Organ Size; Rats; Sesquiterpenes; Spleen; Thymus Gland

Topics: Ascorbic Acid; Female; Humans; Leukocytes; Liver Diseases; Male

Topics: Ascorbic Acid; Avitaminosis; Clinical Enzyme Tests; Diabetes Mellitus; Female; Gastrointestinal Diseases; Hospitalization; Humans; Liver Diseases; Male; Pyridoxine; Riboflavin; Thiamine; Vitamins

Topics: Alcoholism; Ascorbic Acid; Humans; Leukocytes; Liver Cirrhosis, Alcoholic; Liver Diseases

Biochemical evidence of thiamine deficiency was found in 58% of patients with chronic liver disease, the incidence being higher in alcoholic than in non-alcoholic patients. Daily supplementation with high doses of thiamine hydrochloride (200 mg/day) for one week restored levels of thiamine pyrophosphate (TPP), the active co-enzyme form of thiamine, to normal in all cases. Such supplementation also stimulated synthesis of the TPP dependent enzyme transketolase. Because of the essential role of TPP as a co-factor in intermediary metabolism, it is concluded that high doses of thiamine should be included in the routine nutritional management of patients with severe chronic liver disease.

Topics: Ascorbic Acid; Chronic Disease; Erythrocytes; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases; Pyridoxine; Thiamine; Thiamine Deficiency; Transketolase

Biochemical deficiency of thiamine, vitamin B6, ascorbic acid or nicotinic acid occurred in 71% and 88% of patients with fulminant hepatic failure (FHF) and decompensated chronic liver disease (DCLD) respectively. Transient high plasma vitamin B6 concentrations in FHF were followed by low levels later in the illness. Although patients with DCLD of alcoholic aetiology tended to have lower circulating levels of vitamins than those with non-alcoholic DCLD, the prevalence of abnormally low concentrations did not differ. Decreased dietary nutrient intake and alcohol appeared to be less important determinants of biochemical vitamin deficiency than the presence of liver disease per se. Finally, urinary excretion of these vitamins or their major metabolites in patients with severe liver disease correlated poorly with circulating levels of vitamins.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Liver Diseases; Nicotinic Acids; Pyridoxine; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Topics: Ascorbic Acid; Biliary Tract Diseases; Erythrocytes; Humans; In Vitro Techniques; Liver Diseases; Oxidation-Reduction

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Diet; Dimethylamines; Dimethylnitrosamine; Gastric Mucosa; Liver; Liver Diseases; Male; Nitrites; Ornithine Carbamoyltransferase; Phenols; Rats

Topics: Acute Disease; Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Chronic Disease; Female; Growth Disorders; Hematuria; Humans; Infant, Newborn; Liver; Liver Diseases; Male; Methionine; Pregnancy; Tyrosine

Topics: Alanine Transaminase; Aminopyrine; Animals; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Dimethylnitrosamine; Liver; Liver Diseases; Necrosis; Nitrites; Nitrosamines; Rats

1. Hepatic alcohol dehydrogenase activity and leucocyte ascorbic acid content was measured in thirty-five patients with liver disease and in ten control subjects with duodenal ulcer. The patients with liver disease were divided into three groups consisting of non-drinkers, moderate drinkers and alcoholic/heavy drinkers. 2. There was no significant difference in hepatic alcohol dehydrogenase activity between the groups with liver disease, but all patients had less than half the hepatic alcohol dehydrogenase activity of the control subjects (P less than 0-001). 3. The ascorbic acid in leucocytes was significantly lower in the alcoholic/heavy drinker group than that in the control subjects (P less than 0-02) when the Student's t-test was applied, but no significant difference was found when the Mann-Whitney U-test was used. 4. A correlation coefficient of r = 0-77 (P less than 0-001) was observed among the thirty-five patients with liver disease when hepatic alcohol dehydrogenase activity was compared with leucocyte ascorbic acid content. An insignificant correlation (r = 0-332) was found in the control subjects with no liver disease. 5. This comparison was also significant among non-drinkers with liver disease (r = 0-873; P less than 0-001), moderate drinkers (r = 0-739; P less than 0-02) and alcoholic/heavy drinkers (r = 0-702; P less than 0-005). 6. The addition of ascorbic acid in vitro (0-5-10 mmol/1) had no effect on the activity of alcohol dehydrogenase. 7. The relation between hepatic alcohol dehydrogenase activity and leucocyte ascorbic acid content is probably a consequence of liver disease, as opposed to any specific effect of ascorbic acid deficiency of alcohol consumption on alcohol dehydrogenase activity.

Topics: Alanine Transaminase; Alcohol Drinking; Alcohol Oxidoreductases; Ascorbic Acid; Aspartate Aminotransferases; Female; Humans; Leukocytes; Liver; Liver Diseases; Male

Topics: Administration, Oral; Alcohol Oxidoreductases; Ascorbic Acid; Ethanol; Humans; Leukocytes; Liver; Liver Diseases; Male; Metabolic Clearance Rate; Time Factors

Topics: Adolescent; Adult; Aged; Anemia; Ascorbic Acid; Child, Preschool; Deferoxamine; Drug Therapy, Combination; Female; Humans; Iron; Liver Diseases; Lymphoma; Male; Middle Aged

Topics: Ascorbic Acid; Bilirubin; Humans; Liver Diseases; Male; Oxalates; Self Medication

Topics: Adolescent; Adult; Aged; Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Female; Hair; Hemoglobins; Hospitalization; Humans; Liver Diseases; Male; Middle Aged; Nutrition Disorders; Peptic Ulcer; Protein Deficiency; Proteins; Rehabilitation, Vocational; Serum Albumin; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

Topics: Anemia, Hemolytic; Anemia, Hypochromic; Ascorbic Acid; Bilirubin; Blood Transfusion; Catalase; Chronic Disease; Glomerulonephritis; Gout; Hemoglobinometry; Humans; Iron; Kidney Diseases; Liver Diseases; Nephritis; Nitrogen; Rheumatic Fever; Surgical Procedures, Operative

Topics: Animals; Ascorbic Acid; Atropa belladonna; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Drug Synergism; Liver; Liver Diseases; Liver Regeneration; Mice; Nicotinic Acids; Phytotherapy; Plants, Medicinal; Plants, Toxic; Vitamin E

Topics: Animals; Ascorbic Acid; Azo Compounds; Body Weight; Chemical and Drug Induced Liver Injury; Female; Food Additives; Food Preferences; Hyperplasia; Leukocyte Count; Liver; Liver Diseases; Lymphocytes; Male; Naphthalenes; Organ Size; Rats; Sulfonic Acids

Topics: Adolescent; Adult; Aged; Anemia; Ascorbic Acid; Cachexia; Child; Female; Herpes Zoster; Humans; Liver Diseases; Male; Middle Aged; Neuralgia; Neuritis; Vascular Diseases; Vitamin B Complex

Topics: Acidosis; Adrenal Glands; Animals; Ascorbic Acid; Catecholamines; Ethionine; Exercise Test; Guinea Pigs; Humans; Liver; Liver Diseases; Male; Mandelic Acids; Sleep Wake Disorders

Topics: Aging; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chlorobutanol; Gossypium; Granulation Tissue; Liver Diseases; Metabolism; Necrosis; Rats; Starvation

Topics: Ascorbic Acid; Fructose; Humans; Liver Diseases; Vitamin B Complex

Topics: Adolescent; Anemia; Ascorbic Acid; Child; Corrinoids; Folic Acid; Geriatrics; Humans; Injections, Intravenous; Liver Diseases; Niacinamide; Syndrome; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Ascorbic Acid; Hyperplasia; Liver Diseases; Liver Regeneration; Metabolism; Rabbits; Research

Topics: Anemia; Anemia, Macrocytic; Ascorbic Acid; Blood Cell Count; Bone Marrow Examination; Erythropoiesis; Folic Acid; Geriatrics; Glutamates; Hematocrit; Hemoglobinometry; Humans; Iron; Liver Diseases; Liver Extracts; Phosphatidylethanolamines; Pyridoxine; Reticulocytes; Sulfobromophthalein; Urine; Vitamin B 12

Topics: Anemia; Arteriosclerosis; Ascorbic Acid; Humans; Intracranial Arteriosclerosis; Liver Diseases; Mental Disorders; Pyridoxine; Vitamins

Topics: Ascorbic Acid; Blood Chemical Analysis; Child; Gastroenteritis; Jaundice; Liver Diseases; Liver Function Tests; Nutrition Disorders; Respiratory Tract Diseases; Rickets

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

Topics: Aging; Ascorbic Acid; Liver Diseases; Liver Regeneration; Rats; Research; Vitamins

Topics: Animals; Ascorbic Acid; Hyperthyroidism; Liver Diseases; Microsomes; Microsomes, Liver; Rats; Thyrotoxicosis

Topics: Alanine Transaminase; Ascorbic Acid; Aspartate Aminotransferases; Blood; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; D-Alanine Transaminase; Hepatitis; Liver Diseases; Rats; Research; Toxicology; Transaminases

Topics: Adrenal Cortex Hormones; Amino Acids; Ascorbic Acid; Corrinoids; Diet; Diet Therapy; Folic Acid; Geriatrics; Hematinics; Humans; Liver Diseases; Liver Extracts; Proteins; Rest; Vitamin B 12

Topics: Ascorbic Acid; Corrinoids; Folic Acid; Liver Diseases; Niacin; Nicotinic Acids; Vitamin B 12; Vitamins

Topics: Ascorbic Acid; Carbon Tetrachloride; Chronic Disease; Folic Acid; Humans; Liver Diseases; Niacinamide; Vitamin B 12; Vitamin K; Vitamins

Topics: Ascorbic Acid; Folic Acid; Humans; Liver Diseases; Niacinamide; Tuberculosis; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Ascorbic Acid; Cholestanes; Humans; Liver Diseases; Vitamin D; Vitamins

Topics: Ascorbic Acid; Folic Acid; Humans; Liver Diseases; Organic Chemicals; Vitamin B Complex; Vitamins

Topics: Ascorbic Acid; Corrinoids; Folic Acid; Humans; Liver Diseases; Niacin; Niacinamide; Nicotinic Acids; Proteins; Vitamin B 12; Vitamins

Topics: Ascorbic Acid; Child; Corrinoids; Folic Acid; Infant; Liver Diseases; Niacin; Niacinamide; Nicotinic Acids; Vitamin B 12; Vitamins

Topics: Ascorbic Acid; Folic Acid; Humans; Liver Diseases; Niacin; Niacinamide; Nicotinic Acids; Vitamin B 12; Vitamins

Topics: Ascorbic Acid; Humans; Liver Diseases; Scurvy; Vitamins

Topics: Ascorbic Acid; Humans; Liver Diseases; Metabolic Diseases

Topics: Ascorbic Acid; Histocytochemistry; Humans; Liver Diseases

Topics: Ascorbic Acid; Carbohydrate Metabolism; Glutathione; Humans; Liver; Liver Diseases

Topics: Ascorbic Acid; Biochemical Phenomena; Humans; Liver Diseases; Pyruvates; Pyruvic Acid; Vitamins

Topics: Ascorbic Acid; Carbohydrate Metabolism; Health Resorts; Humans; Liver Diseases; Mineral Waters; Minerals; Water