Stereoselective toxicity of acetochlor chiral isomers on the nervous system of zebrafish larvae

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. Fascinatingly, we observed a remarkable recovery in the S-ACT-induced abnormalities in BBB, neurodevelopment, and behavior in zebrafish larvae upon supplementation of the Wnt/β-catenin signaling pathway. This observation strongly suggests that the Wnt/β-catenin signaling pathway serves as a major target of S-ACT-induced neurotoxicity in zebrafish larvae. In conclusion, S-ACT significantly influences zebrafish larval neurodevelopment by inhibiting the Wnt/β-catenin signaling pathway, distinguishing it from R-ACT neurotoxic effects.