Substrate induction of bilirubin conjugation and biliary excretion in the rat

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Abstract
1. The effect of high bilirubin loads (60 μmol/kg twice daily for 2 days) on glucuronosyltransferase activity and biliary excretion of bilirubin was studied in Wistar rats. 2. The concentration of bilirubin in serum increased from 1.1 μmol/l in controls to 5.5 μmol/l after bilirubin pretreatment. 3. Bilirubin pretreatment led to a 25% increase in hepatic UDP-glucuronosyltransferase activity. Bilirubin Tm, was increased by 22% and correlated positively with glucuronosyltransferase activity. 4. The output of conjugated bilirubin in bile was enhanced but no changes in the proportion of monoconjugates to diconjugates were observed. 5. Our data suggest that prolonged treatment with bilirubin can increase biliary bilirubin excretion by inducing glucuronosyltransferase activity.