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.