State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, PR China; Center of Disease Control and Prevention, PLA, Beijing, PR China.
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, PR China.
Chemosphere. 2022 Apr;293:133522. doi: 10.1016/j.chemosphere.2022.133522. Epub 2022 Jan 4.
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.
蔬菜上经常检测到多种农药残留，这些残留可能会产生个体毒性数据无法预测的联合毒性。由于这些联合效应对食品安全构成了额外的威胁，我们比较了多种农药的个体毒性和联合毒性。多菌灵和毒死蜱是蔬菜中最常检测到的两种农药，先前的研究报告称，联合暴露会导致斑马鱼胚胎协同发育毒性。在这项研究中，我们检测了个体和联合暴露后斑马鱼的运动活动，以评估神经系统毒性。此外，我们还使用转录组学方法来鉴定个体和联合毒性的潜在分子机制。多菌灵单独处理会导致游泳模式紊乱，表现为在光暗转换时角速度、转弯角度、曲折度和加速度增加，而毒死蜱单独处理会降低平均游泳速度和光暗加速度。联合处理显著降低了平均游泳速度和总距离。组合指数表明化合物之间在平均速度和光暗加速度方面具有强烈的拮抗作用。转录组学（RNA-seq）显示，多菌灵显著改变了参与抗原加工和呈递、细胞凋亡、自噬和代谢的基因的表达，包括 ctslb、cyp7a1、hsp70l 和 ugt1a1。相反，毒死蜱显著改变了与各种神经系统相关途径相关的基因，包括谷氨酸能、GABA 能、多巴胺能和钙信号。蛋白质-蛋白质相互作用（PPI）网络分析表明，毒死蜱显著下调了与光转导相关的基因，导致对光暗转换的敏感性降低，而拮抗作用主要反映了在光转导和视黄醇代谢方面的不同影响。多菌灵对 gnat1 和 gngt1 等与视觉相关的基因没有显著影响，而毒死蜱则下调了这些基因的表达，这种下调作用被联合处理所逆转。综合毒性分析必须包括共同施用农药的联合效应，以增强食品安全。
