ETHANOL-RELATED LIVER-INJURY IN THE RAT - A MODEL OF STEATOSIS, INFLAMMATION AND PERICENTRAL FIBROSIS

Background/Aims: While several animal models exist for the study of et hanol heptotoxicity, they are limited in their applicability, This pap er describes a relatively simple rat model of alcohol-related liver in jury. Methods: Ethanol was supplied in the drinking water in a concent ration of 40% v/v for up to 29 weeks, Animals are concurrently supplie d a chow diet which provides adequate protein and choline for normal g rowth, Total fat intake is low (7% of consumed calories). Results: His tological changes of steatosis, inflammation, hepatocyte necrosis and pericentral sclerosis were evident in ethanol-treated rat livers. Litt ermate controls with and without pair-feeding had normal livers, Elect ron microscopy revealed abnormal mitochondria and a marked proliferati on of smooth endoplasmic reticulum in livers of animals fed ethanol, B iochemical analysis revealed that levels of hepatic-free choline were similar in treated and pair-fed control rats, There was an expected in crease in the activity of the microsomal enzyme cytochrome P450 2E1 in ethanol-fed rats. Conclusions: The model provides a convenient method for the production of alcoholic liver injury, and it may be useful fo r the study of the pathogenesis of ethanol-related liver disease. (C) Journal of Hepatology.