Pyrethrum extract induces oxidative DNA damage and AMPK/mTOR-mediated autophagy in SH-SY5Y cells

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.

Keywords: Autophagosomes; Autophagy; Cell viability; DNA damage; Neuroblastoma.