Chronic ethanol and cocaine-induced hepatotoxicity: effects of vitamin E supplementation.
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.
Pirozhkov
S V
SV
Research Institute for Medico-Biological Problems of Addictions, Moscow, Russia.
Eskelson
C D
CD
Watson
R R
RR
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000473:pathology*; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014810:Vitamin E / Q000008:administration & dosage* / Q000378:metabolism
D014810:Vitamin E; D005978:Glutathione; D003042:Cocaine; D001205:Ascorbic Acid; D006909:Hydroxyproline