• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Effect of thiazolidinediones on bile acid transport in rat liver
【24h】

Effect of thiazolidinediones on bile acid transport in rat liver

机译：噻唑烷二酮对大鼠肝脏胆汁酸转运的影响

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The thiazolidinedione derivatives, troglitazone, rosiglitazone, and pioglitazone, are novel insulin-sensitizing drugs that are useful in the treatment of type 2 diabetes. However, hepatotoxicity associated with troglitazone led to its withdrawal from the market in March 2000. In view of case reports of hepatotoxicity from rosiglitazone and pioglitazone, it is unclear whether thiazolidinediones as a class are associated with bepatotoxicity. Although the mechanism of troglitazone-associated hepatotoxicity has not been elucidated, troglitazone and its major metabolite, troglitazone sulfate, competitively inhibit adenosine triphosphate (ATP)-dependent taurocholate transport in isolated rat canalicular liver plasma membrane vesicles mediated by the canalicular bile salt export pump (Bsep). These results suggest that cholestasis may be a factor in troglitazone-associated hepatotoxicity. To determine whether this effect is 1) limited to canalicular bile acid transport and 2) is specific to troglitazone, the effect of troglitazone, rosightazone, and ciglitazone on bile acid transport was examined in rat basolateral (bILPM) and canalicular (cLPM) liver plasma membrane vesicles. In cLPM vesicles, troglitazone, rosiglitazone, and ciglitazone (100 mu M) all significantly inhibited ATP-dependent taurocholate transport. In bILPM vesicles, these three thiazolidinediones also significantly inhibited Na+-dependent taurocholate transport. Inhibition of bile acid transport was concentration dependent and competitive in both cLPM and blLPM vesicles. In conclusion, these findings are consistent with a class effect by thiazolidinediones on hepatic bile acid transport. If hepatotoxicity is associated with this effect, then hepatotoxicity is not limited to troglitazone. Alternatively, if hepatotoxicity is limited to troglitazone, other mechanisms are responsible for its reported hepatotoxicity. (c) 2006 Elsevier Inc. All rights reserved.
机译：噻唑烷二酮衍生物曲格列酮，罗格列酮和吡格列酮是新型的胰岛素敏感性药物，可用于治疗2型糖尿病。然而，与曲格列酮有关的肝毒性导致其在2000年3月退出市场。鉴于罗格列酮和吡格列酮对肝毒性的病例报道，尚不清楚噻唑烷二酮类是否与乙肝毒性有关。尽管尚未阐明曲格列酮相关的肝毒性机制，但曲格列酮及其主要代谢物硫酸曲格列酮硫酸盐竞争性地抑制了由三磷酸腺苷（ATP）依赖性的牛磺胆酸转运，其受大鼠胆汁盐输出泵介导的大鼠小肠肝浆膜小泡（ Bsep）。这些结果表明胆汁淤积可能是曲格列酮相关的肝毒性的一个因素。为了确定这种作用是否是1）限于小管胆汁酸运输和2）特定于曲格列酮，在大鼠基底外侧（bILPM）和小管（cLPM）肝血浆中检查了troglitazone，rosightazone和ciglitazone对胆汁酸运输的影响膜囊泡在cLPM囊泡中，曲格列酮，罗格列酮和西格列酮（100μM）均显着抑制ATP依赖性牛磺胆酸盐的转运。在bILPM囊泡中，这三种噻唑烷二酮也显着抑制了Na +依赖性牛磺胆酸盐的转运。在cLPM和blLPM囊泡中，胆汁酸转运的抑制均与浓度有关且具有竞争性。总之，这些发现与噻唑烷二酮类药物对肝胆汁酸转运的分类作用一致。如果肝毒性与这种作用有关，那么肝毒性不仅限于曲格列酮。或者，如果肝毒性仅限于曲格列酮，则其他机制也可导致其报道的肝毒性。 （c）2006 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号