Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
College of Life Sciences, Shanghai Normal University, Shanghai 200234, China.
Sci Total Environ. 2020 Oct 20;740:139925. doi: 10.1016/j.scitotenv.2020.139925. Epub 2020 Jun 3.
Pyrethrum extract is used to produce the most widely applied botanical pesticides in agriculture. Though it primarily targets voltage-gated sodium channels in pests, its toxic effects in non-target systems, particularly in humans, is unclear. In this study, we investigated potential cytotoxic effects and their underlying mechanisms on human nerve cells in vitro. We found that pyrethrum extract exposure markedly inhibited cell viability and triggered oxidative DNA damage in human SH-SY5Y cells. It also induced LC3-II formation, upregulated Beclin-1 protein production, downregulated p62 protein production, and facilitated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR). These results indicate that cytotoxic exposure to pyrethrum extract could be associated with AMPK/mTOR-mediated autophagy in human nerve cells. Furthermore, the oxidative DNA damage suggests that pyrethrum extract exerts severe toxic effects on human nerve cells. In conclusion, pyrethrum extract carries a risk to human health by inducing cytotoxicity.
除虫菊提取物被用于生产农业中应用最广泛的植物性农药。尽管它主要针对害虫的电压门控钠离子通道，但它在非靶标系统中的毒性作用，特别是在人类中的毒性作用尚不清楚。在这项研究中，我们在体外研究了其对人神经细胞的潜在细胞毒性作用及其潜在机制。我们发现除虫菊提取物暴露显著抑制细胞活力，并在人 SH-SY5Y 细胞中引发氧化 DNA 损伤。它还诱导 LC3-II 形成，上调 Beclin-1 蛋白的产生，下调 p62 蛋白的产生，并促进单磷酸腺苷激活的蛋白激酶 (AMPK)和雷帕霉素的机制靶点 (mTOR)的磷酸化。这些结果表明，除虫菊提取物对人神经细胞的细胞毒性暴露可能与 AMPK/mTOR 介导的自噬有关。此外，氧化 DNA 损伤表明除虫菊提取物对人神经细胞具有严重的毒性作用。总之，除虫菊提取物通过诱导细胞毒性对人类健康构成风险。
