Increased production, hepatic conjugation, and biliary secretion of bilirubin in the rat after chronic ethanol consumption

Abstract

Disturbances of bilirubin metabolism such as jaundice or pigment gallstone formation, or both, occur in alcoholic cirrhosis of the liver. We have studied the influence of chronic ethanol consumption on bilirubin metabolism as well as on biliary calcium and bile acids in 16 pair-fed male rats. The animals received nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 4 wk. Bile flow was significantly enhanced after chronic ethanol feeding (p < 0.05 after 90-min bile collection) and was found to be mainly bile acid-independent. The biliary output and concentration of bilirubin monoconjugates, bilirubin diconjugates, and total calcium was significantly increased (p < 0.01) in alcohol-fed rats compared with controls. This was not the case for unconjugated bilirubin and for the calcium/bile acid ratio. Hepatic bilirubin uridine-5′-diphosphate-glucuronosyltransferase activity (p < 0.01), serum total bilirubin (p < 0.01), and serum free hemoglobin (p < 0.001) were significantly increased after ethanol consumption. These data provide evidence for enhanced bilirubin production, probably due to hemolysis, after alcohol ingestion. The enhanced bile production is associated with an increased hepatic conjugation and subsequent biliary secretion of bilirubin conjugates. In advanced alcoholic liver disease, these compensatory mechanisms may fail and contribute to the development of jaundice.