Alcohol-induced liver injury after jejunoileal bypass operation in rats

The objective of this study was to investigate whether alcohol administration exerts a synergistic effect on jejunoileal bypass-induced liver dysfunction in rats. Male Wistar rats were subjected to 90% jejunoileal bypass or sham operation. For 10 weeks, subgroups were pair-fed either an alcohol-containing (36% of total calories) liquid diet or a liquid diet where alcohol was replaced isocalorically by starch. Alcohol feeding in rats with jejunoileal bypass increased hepatic triglyceride content about 6-fold as compared with bypassed rats receiving control diet. Neither jejunoileal bypass nor alcohol feeding led to significant changes in hepatic DNA and protein contents. Alcohol feeding increased cytochrome P-450 levels both in operated and in sham-operated rats. The administration of alcohol-containing diet decreased the activity of succinic dehydrogenase, the decrease being distinctly more pronounced in rats with jejunoileal bypass than in the sham-operated controls. Light microscopy revealed no significant morphological alterations in liver sections of rats fed the control diet after jejunoileal bypass or of rats receiving either the alcohol-containing diet or the control diet after sham operation. Alcohol feeding in bypassed rats, however, produced marked diffuse accumulation of fat, and regularly led to other histological abnormalities in the liver. These abnormalities included ballooning of hepatocytes and disarray of the trabecular structure of the liver lobule, hyalin inclusions resembling megamitochondria, single-cell necrosis and focal clustering of necrosis, increased number of mitotic figures, and infiltrates with inflammatory cells. The histological lesions of the liver of bypassed rats receiving alcohol exhibited no obvious zonal distribution. The results demonstrate that alcohol feeding to rats subjected to jejunoileal bypass leads to marked liver injury which mimics, at least in part, that of alcohol-induced liver disease in man. Rats subjected to jejunoileal bypass may, therefore, provide a new model for the study of alcoholic liver disease.