Improvement of Estradiol- 17β-D-Glucuronide-Induced Cholestasis by Sodium Tauroursodeoxycholate Therapy in Rats

Publisher Website
Google Scholar
Abstract
Background: Estradiol-17β-D-glucuronide (E-17G), a metabolite of natural estrogen, is well known to cause intrahepatic cholestasis in humans. We therefore investigated the effect of sodium tauroursodeoxycholate (T-UDCA), on E-17G-induced cholestasis in female rats. Methods: For die evaluation of the drug, animals given E-17G (10 µmol/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 the biliary E-17G excretion rate at an early stage after E-17G treatment in rats. However, this drug caused no significant change in the biliary excretion rate of estradiol-3-sulfate-17β-D-glucuronide (E-3S-17G), which is identified as the major biliary metabolite with E-17G throughout me recovery periods. Conclusion: These results suggest that T-UDCA can improve E-17G-induced acute cholestasis by rapidly increasing the biliary E-17G excretion rate. Thus our finding may provide a useful approach for attempts to prevent drug-induced acute cholestasis in humans.