Potentiation of halothane hepatotoxicity by chronic ethanol administration in rat: an animal model of halothane hepatitis.
To determine if chronic ethanol administration modifies the effect of halothane on the liver, fourteen male Wistar rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate (controls) for 6 weeks. After halothane anesthesia of these animals under different oxygen concentration, the livers were examined light microscopically as well as biochemically. The livers from rats fed ethanol which received halothane at low oxygen concentration showed multifocal or patchy necrosis primarily in the centrilobular regions with parenchymal lipid accumulation, whereas no such lesions were not observed in pair-fed controls. Hepatic necrosis was also seen after halothane anesthesia even at ambient oxygen concentrations, although the degree of necrosis was much milder. Hepatic microsomal cytochrome P450 content was increased by 30% after ethanol but was decreased following halothane anesthesia. These data suggest that halothane is hepatotoxic to liver of rats chronically pretreated with ethanol, especially under hypoxic condition.
D000437:Alcoholism / Q000473:pathology; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D006221:Halothane / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D010100:Oxygen; D006221:Halothane