文献类型：期刊文献

英文题名：Stereoselective toxicity of acetochlor chiral isomers on the nervous system of zebrafish larvae

作者：Wang, Xin[1];Li, Shoulin[1];Zhang, Cheng[2];Xu, Wenping[1];Wu, Mengqi[1];Cheng, Jiagao[1];Li, Zhong[1];Tao, Liming[1];Zhang, Yang[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]UT Southwestern Med Ctr, Dept Pathol, Dallas, TX 75390 USA

年份：2024

卷号：464

外文期刊名：JOURNAL OF HAZARDOUS MATERIALS

收录：;EI(收录号：20234815125045);WOS:【SCI-EXPANDED(收录号:WOS:001124588600001)】；

基金：This work was financially Sponsored by the National Key Research and Development Plan (2022YFD1700502) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Acetochlor; Isomer; Nervous; Zebrafish; Wnt/beta-catenin

摘要：Acetochlor (ACT) is a widely detected pesticide globally, and the neurotoxic effects of its chiral isomers on humans and environmental organisms remain uncertain. Zebrafish were used to study the neurotoxicity of ACT and its chiral isomers. Our study reveals that the R-ACT, Rac-ACT, and S-ACT induce neurotoxicity in zebrafish larvae by impairing vascular development and disrupting the blood-brain barrier. These detrimental effects lead to apoptosis in brain cells, hindered development of the central nervous system, and manifest as altered swimming behavior and social interactions in the larvae. Importantly, the neurotoxicity caused by the S-ACT exhibits the most pronounced impact and significantly diverges from the effects induced by the R-ACT. The neurotoxicity associated with the Rac-ACT falls intermediate between that of the R-ACT and S-ACT. Fascinat-ingly, we observed a remarkable recovery in the S-ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/beta-catenin signaling pathway. This observation strongly suggests that the Wnt/beta-catenin signaling pathway serves as a major target of S-ACT-induced neuro-toxicity in zebrafish larvae. In conclusion, S-ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/beta-catenin signaling pathway, distinguishing it from R-ACT neurotoxic effects.