IMPROVEMENT OF ESTRADIOL-17-BETA-D-GLUCURONIDE-INDUCED CHOLESTASIS BYSODIUM TAUROURSODEOXYCHOLATE THERAPY IN RATS

Background: Estradiol-17 beta-D-glucuronide (E-17G), a metabolite of n atural estrogen, is well known to cause intrahepatic cholestasis in hu mans. We therefore investigated the effect of sodium tauroursodeoxycho late (T-UDCA), on E-17G-induced cholestasis in female rats. Methods: F or the evaluation of the drug, animals given E-17G (10 mu mol/kg) were divided into three groups, and T-UDCA was administered intravenously at various doses after E-17G treatment. Results: T-UDCA significantly prevented a marked reduction of bile flow in E-17G-treated rats in all experimental schedules. Furthermore, T-UDCA significantly increased t he biliary E-17G excretion rate at an early stage after E-17G treatmen t in rats. However, this drug caused no significant change in the bili ary excretion rate of estradiol-3-sulfate-17 beta-D-glucuronide (E-3S- 17G), which is identified as the major biliary metabolite with E-17G t hroughout the recovery periods. Conclusion: These results suggest that T-UDCA can improve E-17G-induced acute cholestasis by rapidly increas ing the biliary E-17G excretion rate. Thus our finding may provide a u seful approach for attempts to prevent drug-induced acute cholestasis in humans.