牛磺熊去氧胆酸钠治疗对大鼠雌二醇 -17β -D -葡萄糖醛酸苷诱导的胆汁淤积的改善作用

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

作者信息

Kinbara S, Ishizaki K, Sakakura H, Hirabayashi N, Kasai H, Araki T

机构信息

Pharmacological Research Laboratory, Tokyo Tanabe Co. Ltd., Japan.

出版信息

Scand J Gastroenterol. 1997 Sep;32(9):947-52. doi: 10.3109/00365529709011207.

DOI:10.3109/00365529709011207

PMID:9299676

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.

摘要

背景

17β -D-葡萄糖醛酸雌二醇（E-17G）是天然雌激素的一种代谢产物，众所周知，它会导致人类肝内胆汁淤积。因此，我们研究了牛磺熊去氧胆酸钠（T-UDCA）对E-17G诱导的雌性大鼠胆汁淤积的影响。

方法

为了评估该药物，给予E-17G（10 μmol/kg）的动物被分为三组，在E-17G处理后，以不同剂量静脉注射T-UDCA。

结果

在所有实验方案中，T-UDCA均显著防止了E-17G处理的大鼠胆汁流量的显著减少。此外，T-UDCA显著提高了大鼠在E-17G处理后早期胆汁中E-17G的排泄率。然而，在整个恢复期，该药物对雌二醇-3-硫酸酯-17β -D-葡萄糖醛酸（E-3S-17G）的胆汁排泄率没有显著影响，E-3S-17G是与E-17G一起被确定为主要胆汁代谢产物的物质。