Alcoholic liver injury: experimental models 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 upon 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). Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis), and differed strikingly from the alterations produced by other models of liver injury. 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; D004195:Disease Models, Animal; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology*; D008992:Monkey Diseases; D010215:Papio; D004364:Pharmaceutical Preparations; D051381:Rats; D012376:Rodent Diseases; D013045:Species Specificity; D019966:Substance-Related Disorders
D008074:Lipoproteins; D004364:Pharmaceutical Preparations; D000431:Ethanol