Yang Yun, Wei Xiaoyi, Ying Mengchao, Huang Haiyan, Sha Yijie, Hong Xinyu, Xiao Ping, Tao Gonghua
Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China.
State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai 200233, China.
Toxics. 2024 Mar 30;12(4):258. doi: 10.3390/toxics12040258.
Natural pyrethrins (NPs), one kind of bio-pesticide, have been widely used in organic agriculture and ecological environment studies. Studies have shown that NPs may affect the metabolism of rat liver and human hepatocytes; nevertheless, the toxic effects of NPs on the liver and the related mechanisms are still incompletely understood. In this research, we utilized three types of human liver cells to investigate the mechanism of NPs' induction of oxidative stress. The results showed that NPs exhibit noteworthy cytotoxic effects on human liver cells. These effects are characterized by the induction of LDH release, mitochondrial collapse, and an increased production of ROS and MDA content, subsequently activating the Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2- related factor 2 (Keap1/Nrf-2) pathway. The ROS inhibitor N-acetyl-L-cysteine (NAC) can alleviate ROS/Nrf2-mediated oxidative stress. In addition, the siRNA knockdown of Nrf-2 exacerbated the injury, including ROS production, and inhibited cell viability. In summary, the ROS-mediated Keap1/Nrf-2 pathway could be an important regulator of NP-induced damage in human liver cells, which further illustrates the hepatotoxicity of NPs and thereby contributes to the scientific basis for further exploration.
天然除虫菊酯（NPs）作为一种生物农药，已广泛应用于有机农业和生态环境研究中。研究表明，NPs可能会影响大鼠肝脏和人类肝细胞的代谢；然而，NPs对肝脏的毒性作用及其相关机制仍未完全明确。在本研究中，我们利用三种类型的人类肝细胞来探究NPs诱导氧化应激的机制。结果表明，NPs对人类肝细胞具有显著的细胞毒性作用。这些作用表现为诱导乳酸脱氢酶（LDH）释放、线粒体崩溃以及活性氧（ROS）生成增加和丙二醛（MDA）含量升高，随后激活 Kelch样ECH相关蛋白1/核因子红细胞2相关因子2（Keap1/Nrf-2）通路。ROS抑制剂N-乙酰-L-半胱氨酸（NAC）可减轻ROS/Nrf2介导的氧化应激。此外，Nrf-2的小干扰RNA（siRNA）敲低加剧了包括ROS生成在内的损伤，并抑制细胞活力。总之，ROS介导的Keap1/Nrf-2通路可能是NPs诱导人类肝细胞损伤的重要调节因子，这进一步阐明了NPs的肝毒性，从而为进一步探索提供了科学依据。
