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8-epidiosbulbin E乙酸通过线粒体和内质网膜之间的代谢激活中介交叉声触发了亡
Shiyu Zhang1, Bowen Gong2, Rong Tan1
1The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, PR China.
来自 Dioscorea bulbifera L. 的 8-epidiosbulbin E 酸盐 (EEA) 通过形成反应性代谢物引起肝损伤. 通过破坏线粒体和内分泌网膜通路,EEA会诱导肝细胞的亡.
科学领域:
- 肝毒性 肝毒性 肝毒性
- 分子毒理学 分子毒理学
- 自然产品化学 自然产品化学
背景情况:
- 8-埃皮迪奥斯布尔宾E乙酸 (EEA) 是来自Dioscorea bulbifera L.的一种双类乳.
- 欧洲经济区已与小鼠的肝损伤有关.
- 由CYP3A介导的代谢激活是EEA诱导的毒性的一种拟议机制.
研究的目的:
- 为了研究EEA诱导的肝损伤的机制.
- 检查线粒体和内分泌网膜 (ER) 途径在EEA毒性的作用.
- 评估潜在的防护剂对EEA诱导的亡.
主要方法:
- 主要小鼠肝细胞暴露于不同度的EEA (25200μM).
- 通过测量线粒体和ER通路蛋白水平的变化来评估亡.
- 肝细胞被预先用可纳,维生素C,谷氨乙烯,4-甲酸或L-布氨酸硫胺进行治疗.
主要成果:
- 在初级肝细胞中,EEA暴露诱导了亡.
- 欧洲环境署改变了线粒体和ER通路中的蛋白质水平.
- 凯托可纳,维生素C,谷氨乙烯和4-黄油酸降低了亡.
- L-布氨酸硫胺加剧了EEA诱导的亡.
- 代谢激活,谷氨 (GSH) 枯竭和活性氧物种 (ROS) 都与此有关.
结论:
- 通过破坏线粒体和ER通路的交叉交互,EEA会诱导初级肝细胞的亡.
- 通过CYP3A介导的代谢激活对于EEA毒性至关重要.
- 减少GSH和ROS有助于EEA诱导的亡.
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