通过线粒体损伤介导的自性介导的脊柱体诱导潜在的神经毒性
1Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Molecules (Basel, Switzerland)
|January 11, 2024
概括
暴露于Spinetoram杀虫剂会损害人类细胞和斑马鱼,通过线粒体损伤和自会引起神经毒性. 这项研究强调了这种广泛使用的农业化学品的潜在风险,并为安全评估提供了信息.
科学领域:
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 斯宾尼托拉姆是一种半合成杀虫剂,向昆虫的乙胆受体.
- 尽管在农业中使用,但其在人类中的神经毒性仍未得到充分研究.
研究的目的:
- 为了研究spinetoram对人类神经母细胞瘤细胞 (SH-SY5Y) 和斑马鱼的神经毒性作用.
- 要阐明背后的机制spinetoram诱导的神经毒性,专注于线粒体功能和自.
主要方法:
- 将SH-SY5Y细胞暴露在不同度的脊柱膜中 (520μM).
- 评估细胞活力,氧化应激,线粒体膜潜力 (ΔΨm) 和ATP合成.
- 对自标记物 (LC3,p62,beclin-1) 和AMPK/mTOR信号通路的分析.
- 在暴露于spinetoram的斑马鱼 (520μg/mL) 中进行神经行为观察和自分析.
主要成果:
- 斯宾尼托拉姆抑制了细胞活力,诱导了氧化应激,并在SH-SY5Y细胞中引起线粒体功能障碍 (ΔΨm崩,mPTP开放,ATP降低,Ca2+过载).
- 在细胞培养和斑马鱼中,Spinetoram通过AMPK/mTOR途径触发了自.
- 斑马鱼表现出神经行为缺陷,包括运动减少和尾巴摆动,与观察到的自相关.
结论:
- 斯宾尼托拉姆暴露在体外和体内都会引起显著的神经毒性.
- 线粒体损伤和随后的自是spinetoram神经毒性作用的关键机制.
- 这些发现为人类的脊柱膜安全性评估提供了关键数据.
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