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Antagonistic effects and mechanisms of carbendazim and chlorpyrifos on the neurobehavior of larval zebrafish

斑马鱼 生物 多菌灵 毒死蜱 毒性 转录组 多巴胺能 杀虫剂 药理学 基因表达 生物化学 基因 内分泌学 内科学 植物 多巴胺 生态学 杀菌剂 医学
作者
Wanjun Zhang,Ruiqi Fan,Sunlin Luo,Ying Liu,Yongpeng Jin,Yongchen Li,Mengqin Xiong,Xiaoyan Yuan,Jia Li,Yiqiang Chen
出处
期刊:Chemosphere [Elsevier BV]
卷期号:293: 133522-133522 被引量:6
标识
DOI:10.1016/j.chemosphere.2022.133522
摘要

Residues from multiple pesticides are frequently detected on vegetables, which may produce combined toxicity not predicted by individual toxicity data. As these combined effects present additional dangers to food safety, we have compared individual to combined effects for a variety of pesticides. Carbendazim and chlorpyrifos are the two most commonly detected pesticides in vegetables, and previous studies reported that combined exposure results in synergistic developmental toxicity to zebrafish embryos. In this study, individual and combined effects on zebrafish motor activity were examined following individual and combined exposure to assess nervous system toxicity. Further, transcriptomics methods were used to identify potential molecular mechanisms for individual and combined toxicity. Carbendazim alone induced a disorganized swim pattern characterized by increased angular velocity, turn angle, meander, and acceleration during light-dark transition, while chlorpyrifos alone reduced average swim speed and light-dark acceleration. Combined treatment significantly reduced average swim velocity and total distance traveled. Combination indices indicated strong antagonism between compounds for average speed and light-dark acceleration. Transcriptomics (RNA-seq) showed that carbendazim significantly altered the expression of genes involved in antigen processing and presentation, apoptosis, autophagy, and metabolism, including ctslb, cyp7a1, hsp70l, and ugt1a1. Alternatively, chlorpyrifos significantly altered genes involved in various nervous system-related pathways, including glutamatergic, GABAergic, dopaminergic, and calcium signaling. Protein-protein interaction (PPI) network analysis suggested that chlorpyrifos significantly downregulated genes related to light transduction, resulting in decreased sensitivity to light-dark transitions, while antagonism mainly reflected divergent effects on phototransduction and retinol metabolism. Carbendazim had no significant effects on vision-related genes such as gnat1 and gngt1, while chlorpyrifos downregulated expression, an effect reversed by the combination. Comprehensive toxicity analyses must include joint effects of co-applied pesticides for enhanced food safety.
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