1. Improvement of estradiol-17 beta-D-glucuronide-induced cholestasis by sodium tauroursodeoxycholate therapy in rats
- Author
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H Kasai, N Hirabayashi, T Araki, K Ishizaki, H Sakakura, and S Kinbara
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Metabolite ,Taurochenodeoxycholic acid ,Biology ,Excretion ,Bile Acids and Salts ,Rats, Sprague-Dawley ,Taurochenodeoxycholic Acid ,chemistry.chemical_compound ,Cholestasis ,Internal medicine ,medicine ,Animals ,Bile ,Bile acid ,Estradiol ,Ursodeoxycholic Acid ,Gastroenterology ,medicine.disease ,Ursodeoxycholic acid ,Rats ,Endocrinology ,chemistry ,Estrogen ,Female ,Glucuronide ,medicine.drug - Abstract
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.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.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.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.
- Published
- 1997