Enhancement of cocaine-induced hepatotoxicity by ethanol.
The contribution of moderate ethanol consumption on cocaine induced hepatotoxicity and the role lipid peroxidation plays as a possible mechanism of such increased hepatotoxicity were evaluated. Male C57BL/6 mice were injected interperitoneally (i.p.) with increasing doses of cocaine, from 10 to 50 mg/kg body weight daily and simultaneously fed a liquid diet containing 28% of the calories as ethanol for 5 or 9 weeks. Control mice received saline (i.p.) and an isocaloric carbohydrate diet. Lipid fluorescence and conjugated dienes of extracted lipids and amounts of malondialdehyde (MDA) were evaluated as indices of lipoperoxidation. In addition, serum alanine aminotransferase and aspartate transaminase were measured as indicators of liver injury and cellular death. After 9 weeks, ethanol consumption during cocaine treatment increased hepatic lipid fluorescence, conjugated dienes and MDA about twofold over mice-treated with cocaine alone. Similarly, serum transaminases were 2.8-6-fold greater in mice consuming alcohol and treated with cocaine than in mice treated with cocaine only. Histological examination of livers from mice fed ethanol during treatment with cocaine exhibited increased hepatic injuries and necrosis. The data suggest that ethanol exacerbates cocaine-induced hepatotoxicity via increases in free radical activity and hepatic lipid peroxidation.
Odeleye
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Department of Family and Community Medicine, Arizona Health Sciences Center, University of Arizona, Tucson 85724.
Watson
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Eskelson
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Earnest
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D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003042:Cocaine / Q000493:pharmacokinetics / Q000633:toxicity*; D004357:Drug Synergism; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D006519:Hepatitis, Alcoholic / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010743:Phospholipids / Q000378:metabolism
D010743:Phospholipids; D000431:Ethanol; D008315:Malondialdehyde; D003042:Cocaine