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由乙胺及其性异构体诱导的心脏毒性的分子机制
Xin Wang1, Li Geng1, Mengqi Wu1
1Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
The Science of the total environment
|August 20, 2023
概括
性同位素 (+) -S-乙胺 (ACT) 是心脏毒性的主要原因,诱导DNA损伤和心肌细胞的亡. 这凸显了与性农药相关的风险.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 心血管生物学 心血管生物学
背景情况:
- 乙胺 (ACT) 被广泛用作一种种族混合物.
- 环境中的ACT残留物引起了人们的健康问题.
- ACT的基拉尔异构体可能表现出差异性毒性.
研究的目的:
- 为了研究乙胺及其性异构体的心脏毒性.
- 为了确定负责心脏毒性的特定异构体.
- 阐明ACT诱导心脏毒性背后的分子机制.
主要方法:
- 在实验室中使用人类心肌细胞 (AC16) 细胞系进行毒性评估.
- 使用斑马鱼胚胎心脏进行体内毒性评估.
- 对DNA损伤,亡,活性氧物种 (ROS),线粒体膜潜力 (MMP) 和酶激活的分析.
主要成果:
- (+) -S-乙胺 (ACT) 被确定为主要的心脏毒性成分.
- 两种R-和S-异构体都诱导了AC16细胞中的DNA损伤,亡和ROS产生.
- 斑马鱼研究证实 (+) -S-ACT诱导的酶-3激活和DNA损伤 (γH2AX).
结论:
- (+) -S-乙胺是种族性ACT心脏毒性的主要驱动因素.
- 该机制涉及ROS生成,线粒体功能障碍和亡.
- 这些发现强调了需要对手性农药进行风险评估的必要性.
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