通过Nrf-2信号通路,在人类肝细胞中产生天然氨酸诱导的氧化损伤
Yun Yang1,2, Xiaoyi Wei3, Mengchao Ying1,2
1Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China.
Toxics
|April 26, 2024
概括
通过Keap1/Nrf-2通路诱导氧化应激,自然素 (NP) 会导致肝细胞损伤. 这项研究阐明了NP肝毒性机制,这对于了解生物农药安全性至关重要.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 环境科学 环境科学
背景情况:
- 天然甲 (NPs) 是农业中广泛使用的生物杀虫剂.
- 已知NP对肝脏代谢的潜在影响,但机制尚不清楚.
- 了解NP肝毒性对于安全性评估至关重要.
研究的目的:
- 研究人类肝细胞中NP诱导的氧化应激机制.
- 阐明Keap1/Nrf-2通路在NP毒性的作用.
- 为评估NP安全提供科学基础.
主要方法:
- 使用了三个人类肝脏细胞系.
- 评估了细胞毒性,包括LDH释放和线粒体崩.
- 测量了反应性氧物种 (ROS) 和麦隆迪甲 (MDA) 的含量.
- 研究了Keap1/Nrf-2通路的激活和Nrf-2的淘汰效应.
- 使用N-乙-L-氨酸 (NAC) 作为ROS抑制剂.
主要成果:
- 在人类肝细胞中,NP诱导了显著的细胞毒性作用.
- 观察到ROS和MDA产量的增加,以及线粒体功能障碍.
- NP激活了凯尔奇类ECH相关蛋白1/核因子红色素2-相关因子2 (Keap1/Nrf-2) 途径.
- 通过NAC减轻ROS抑制NP诱导的氧化应激.
- Nrf-2倒置加剧了NP诱导的肝细胞损伤.
结论:
- 通过ROS介导的Keap1/Nrf-2通路是人类肝细胞NP诱导损伤的关键调节者.
- NP表现出显著的肝毒性,由氧化应激介导.
- 这些发现有助于对NP毒理学和安全性的科学理解.
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