...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Molecular mechanism of 17α-ethinylestradiol cytotoxicity in isolated rat hepatocytes
【24h】

Molecular mechanism of 17α-ethinylestradiol cytotoxicity in isolated rat hepatocytes

机译：分离的大鼠肝细胞中17α-炔雌醇细胞毒性的分子机制

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

17α-Ethinylestradiol (17-EE) is used in formulations of contraceptives and hormone replacement therapy because it is an estradiol derivative. However, it has been associated with an increase in the risk of liver cancers and injury. The carcinogenic properties of 17-EE are similar to that of other estrogens, but the molecular mechanism of liver injury is still unclear. It is important to identify any secondary toxic mechanisms that can be used to prevent or treat the toxicity. The LC50 of 17-EE toward isolated rat hepatocytes was determined to be 150 ± 8 μmol/L. Accelerated cytotoxicity mechanism screening (ACMS) techniques using isolated rat hepatocytes showed that CYP1A inhibitors decreased cytotoxicity, whereas tyrosinase increased toxicity; this suggests that the toxic mechanism involved is the oxidation of 17-EE. A hepatocyte inflammation model also increased 17-EE-induced mitochondrial toxicity, as well as the formation of ROS and H2O2. Cytotoxicity was increased when inhibitors of quinone reduction, catechol-O-methylation, glucuronidation, glutathione conjugation, and sulfation were co-incubated with 17-EE. The hepatocytes could be rescued with antioxidants and quinone trapping agents, thereby suggesting a role for quinoid moiety induced oxidative stress in 17-EE induced cytotoxicity. These mechanisms for 17-EE hepatotoxicity could provide a new perspective for the treating 17-EE-induced liver injury.
机译：17α-乙炔雌二醇（17-EE）是一种雌二醇衍生物，可用于避孕药和激素替代疗法。然而，它与肝癌和受伤风险的增加有关。 17-EE的致癌特性与其他雌激素相似，但尚不清楚肝损伤的分子机制。重要的是要确定可用于预防或治疗毒性的任何次级毒性机制。测定17-EE对分离的大鼠肝细胞的LC50为150±8μmol/ L。使用分离的大鼠肝细胞的加速细胞毒性机制筛选（ACMS）技术显示，CYP1A抑制剂可降低细胞毒性，而酪氨酸酶则可增加毒性。这表明所涉及的毒性机制是17-EE的氧化。肝细胞炎症模型还增加了17-EE诱导的线粒体毒性，以及ROS和H2O2的形成。当将醌还原，儿茶酚-O-甲基化，葡糖醛酸化，谷胱甘肽结合和硫酸化抑制剂与17-EE共同孵育时，细胞毒性增加。可以用抗氧化剂和醌捕获剂拯救肝细胞，从而表明在17-EE诱导的细胞毒性中，醌型诱导氧化应激的作用。这些17-EE肝毒性机制可为治疗17-EE引起的肝损伤提供新的视角。

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