文献类型：期刊文献

英文题名：Spinetoram-Induced Potential Neurotoxicity through Autophagy Mediated by Mitochondrial Damage

作者：Chen, Fan[1];Lu, Jin[1];Li, Meng[1];Yang, Junwu[2];Xu, Wenping[1];Jiang, Xufeng[3];Zhang, Yang[1];Richardson, Rudy J.

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Frog Prince Fujian Baby&Child Care Prod Co Ltd, Zhangzhou 363000, Peoples R China;[3]Ugel Cosmet PTE Ltd, Singapore 349561, Singapore

年份：2024

卷号：29

期号：1

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001140697700001)】；

基金：No Statement Available

语种：英文

外文关键词：spinetoram; neurotoxicity; autophagy; human SH-SY5Y cell line; zebrafish; risk assessment

摘要：Spinetoram is an important semi-synthetic insecticide extensively applied in agriculture. It is neurotoxic to insects, primarily by acting on acetylcholine receptors (nAChRs). However, few studies have examined the neurotoxicity of spinetoram in human beings. In this study, various concentrations (5, 10, 15, and 20 mu M) of spinetoram were employed to expose SH-SY5Y cells in order to study the neurotoxic effects of spinetoram. The results showed that spinetoram exposure markedly inhibited cell viability and induced oxidative stress. It also induced mitochondrial membrane potential collapse (Delta psi m), and then caused a massive opening of the mitochondrial permeability transition pore (mPTP), a decrease in ATP synthesis, and Ca2+ overloading. Furthermore, spinetoram exposure induced cellular autophagy, as evidenced by the formation of autophagosomes, the conversion of LC3-I into LC3-II, down-regulation of p62, and up-regulation of beclin-1. In addition, we observed that p-mTOR expression decreased, while p-AMPK expression increased when exposed to spinetoram, indicating spinetoram triggered AMPK/mTOR-mediated autophagy. Complementarily, the effect of spinetoram on neurobehavior was studied using the zebrafish model. After being exposed to different concentrations (5, 10, and 20 mu g/mL) of spinetoram, zebrafish showed neurobehavioral irregularities, such as reduced frequency of tail swings and spontaneous movements. Similarly, autophagy was also observed in zebrafish. In conclusion, spinetoram exposure produced potential neurotoxicity through autophagy mediated by mitochondrial damage. The experimental data and results of the neurotoxicity study of spinetoram provided above are intended to serve as reference for its safety assessment.