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Environmental metconazole exposure triggers enantiomer-specific neurotoxicity in zebrafish larvae: Mechanistic links between synergistic neurotransmitter dysregulation and behavioral deficits

文献类型： 外文期刊

作者： Lulu Liu;Mengying Zhao;Lin Li;Yifan Zhang;Lin Yang;Zhiqiang Kong;Minmin Li

作者机构：

关键词： Ecological hazards;Homeostasis;Stereoselective neurotoxicity;Synergistic dysregulation;Triazole fungicide

期刊名称： Journal of Hazardous Materials

ISSN： 1873-3336

年卷期： 2025 年 499 卷

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

摘要： Metconazole (MEZ) is a chiral triazole fungicide frequently detected in aquatic ecosystems. Nevertheless, its potential neurotoxic effects during the critical developmental windows of aquatic organisms remain poorly understood, particularly with respect to individual enantiomers. In this study, we examined the neurotoxicity of MEZ (0.02–4 mg/L) and its cis-isomer in zebrafish. Exposure to MEZ and its cis-isomers induced enantiomer-specific neurobehavioral dysfunction, characterized by locomotor suppression (15.5–75.4 % reduction), histopathological brain damage, and neuronal loss (0.5 %-81.0 % reduction) in Tg (elavl3:EGFP) larvae. Integrated transcriptomic and metabolomic analyses revealed stereoselective disruption of dopaminergic, GABAergic, and cholinergic pathways. Specifically, rac-MEZ exposure significantly reduced levels of dopamine (10.1 %), γ-aminobutyric acid (12 %), and acetyl-CoA (14 %). Synergistic enantiomer interactions exacerbated neurotoxicity beyond additive predictions, downregulating drd (dopamine receptor), gabbr (GABA receptor), and grm (glutamate receptor) expression, while impairing synaptic plasticity via CREB signaling inhibition. Crucially, rac-MEZ elicited stronger neurotoxicity than individual cis-isomers, demonstrating that enantiomer synergism—not merely additive effects—drives hazard amplification. These findings provide a mechanistic explanation for MEZ-induced neurotoxicity, including transcriptional-metabolic disturbances, neurotransmitter imbalance, and compromised synaptic plasticity. This study significantly advances the understanding of stereoselective toxicity mechanisms and establishes a framework for assessing the neurotoxicity of chiral environmental contaminants.

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