Improvement of estradiol-17 beta-D-glucuronide-induced cholestasis by sodium tauroursodeoxycholate therapy in rats

  • Scand J Gastroenterol. 1997 Sep;32(9):947-52. doi: 10.3109/00365529709011207.
S Kinbara  1 ,  K Ishizaki ,  H Sakakura ,  N Hirabayashi ,  H Kasai ,  T Araki
Affiliations
  • 1. Pharmacological Research Laboratory, Tokyo Tanabe Co. Ltd., Japan.
PMID: 9299676 DOI: 10.3109/00365529709011207
Abstract

Background: Estradiol-17 beta-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 the evaluation of the drug, Animals given E-17G (10 mumol/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 in 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-17 beta-D-glucuronide (E-3S-17G), which is identified as the major biliary metabolite with E-17G throughout the 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.

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