在Channa argus中,急性水性暴露会诱导肝脏铁亡
Xingyu Chen1, Wenqian Sun1, Yanting Song1
1Faculty of Resources and Environmental Science, Hubei University, Wuhan 430062, China; Hubei Key Laboratory of Regional Development and Environmental Response, Hubei University, Wuhan 430062, China.
Ecotoxicology and environmental safety
|August 30, 2024
概括
(Cd) 毒性通过抑制Nrf2/Keap1通路,诱导鱼肝中的铁和肝胆. 这项研究揭示了水生生物中Cd毒性的新机制.
科学领域:
- 环境毒理学环境毒理学
- 鱼类生物学 鱼类生物学
- 细胞应激反应的应激反应
背景情况:
- (Cd) 是一种有毒的重金属,对水生生态系统构成风险.
- 之前的研究将鱼肝中Cd暴露与自,亡和内质网膜应激联系起来.
- 铁和特定信号通路在Cd诱导的鱼肝损伤中的作用仍然不清楚.
研究的目的:
- 为了研究Channa argus肝脏中Cd毒性的机制.
- 为了确定铁死是否参与Cd诱导的鱼肝损伤.
- 阐明Nrf2/Keap1信号通路在Cd毒性和肝硬化症中的作用.
主要方法:
- 在96小时内,将Channa argus暴露在Cd (0,1.0,2.0 mg/L) 的不同度下.
- 评估肝脏组织结构,线粒体完整性和氧化应激和铁亡的生化标志物.
- 对关键铁和Nrf2/Keap1通路相关基因的mRNA表达水平的分析.
主要成果:
- 暴露于Cd破坏了肝脏线粒体和诱导铁亡,由改变的Fe2+,ROS,MDA,费里丁,GSH和脂质过氧化标志物证明.
- 观察到铁灭基因 (gpx4,slc7a11) 的下调和Nrf2/Keap1通路的抑制 (上调的keap1a/b,下调的nrf2,ho-1,nqo1,cat).
- 暴露于Cd导致肝硬化症,其特征是脂质积累和改变的脂质新陈代谢,也由Nrf2/Keap1通路调节.
结论:
- 铁亡是水中Cd诱导的鱼类肝损伤的关键机制,通过Nrf2/Keap1信号通路进行介导.
- 鱼类中Cd诱导的肝肥胖症也通过Nrf2/Keap1通路进行调节.
- 这些发现为鱼肝中Cd毒性的分子基础提供了新的见解.
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