Animal models of ethanol dependence and liver injury in rats and baboons.
A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence on withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver, and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.
D000437:Alcoholism / Q000150:complications*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D006520:Hepatitis, Animal / Q000209:etiology; D006801:Humans; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced*; D010215:Papio; D051381:Rats; D013375:Substance Withdrawal Syndrome; D013997:Time Factors