ascorbic-acid and Hepatitis--Alcoholic

We studied the effect of administering glycine on tissue lipid peroxidation and enzymic and non-enzymic antioxidants in experimental hepatotoxic Wistar rats. Hepatotoxicity was induced by administering ethanol for 30 days by intragastric intubation. Glycine administered at a dose of 0.6 g kg(-1) body weight for 30 days significantly inhibited the severe oxidative stress as evidenced by the decreased levels of liver and brain thiobarbituric acid reactive substances (TBARS) and hydroperoxides compared to control. The activities of enzymic and non-enzymic antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in the liver and brain were significantly elevated on glycine supplementation as compared to the untreated alcohol fed rats. The levels of serum vitamin E and vitamin C were also increased to near normal levels on glycine treatment. Microscopic examination of alcohol treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol treated rat brain demonstrated oedma, which was significantly lowered on treatment with glycine. Thus our study shows that administering glycine to alcohol supplemented rats, markedly reduced the oxidative stress and elevated the enzymic and non-enzymic antioxidants in the liver and brain, which a was associated with a reversal of hepatic steatosis and cerebral oedma.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Glutathione; Glutathione Peroxidase; Glycine; Hepatitis, Alcoholic; Hydrogen Peroxide; Lipid Peroxidation; Liver; Male; Oxidative Stress; Rats; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

An original experimental model for detecting organ-specific markers of predisposition to ethanol hepatotoxicity is proposed. A relationship between congenital activity of LPO processes in rat liver (before ethanol intoxication) and the type and severity of ethanol-induced damage to the liver was demonstrated using methods of mathematical modeling. It was proven that intact rats with genetically high MDA levels in the liver and more active systems of MDA generation in ascorbate- and NADPH-dependent reactions are prone to ethanol-induced damage to the liver.

Topics: Acetaldehyde; Alanine Transaminase; Animals; Ascorbic Acid; Biomarkers; Biotransformation; Ethanol; Genetic Predisposition to Disease; Hepatitis, Alcoholic; Hepatitis, Animal; Lipid Peroxidation; Male; Malondialdehyde; NADP; Rats

The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short-term exposure of 21 days of treatment.

Topics: Animals; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Cocaine; Dose-Response Relationship, Drug; Drug Synergism; Glutathione; Hepatitis, Alcoholic; Hydroxyproline; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Vitamin E