INHIBITION OF BILIARY GLUTATHIONE EXCRETION BY LITHOCHOLATE-3-O-GLUCURONIDE - A POSSIBLE ROLE IN INITIATING LITHOCHOLATE-3-O-GLUCURONIDE-INDUCED CHOLESTASIS

Lithocholate-3-O-glucuronide is a cholestatic agent. Herein, the effec t of lithocholate-3-O-glucuronide on biliary glutathione excretion, wh ich has been suggested as a driving force for the bile acid independen t canalicular bile flow, was examined in rats. Intravenously injected lithocholate-3-O-glucuronide (1.6 mumol/100 g body wt.) caused a trans itional decrease in bile flow (67% of the basal value) and depressed b iliary glutathione excretion to 15% of the basal value, which correspo nded to biliary lithocholate-3-O-glucuronide excretion. A lower dose o f lithocholate-3-O-glucuronide (1.0 mumol/100 g body wt.) also inhibit ed biliary glutathione excretion (54%) with a slight decrease in bile flow (80%). These findings indicate that a decrease in bile acid indep endent bile flow due to the inhibition of biliary glutathione excretio n is one of the initiating factors to cause cholestasis induced by lit hocholate-3-O-glucuronide.