Hu Yi, Hu Jingying, Li Weihua, Gao Yu, Tian Ying
Center for Biomedical Informatics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China.
J Appl Toxicol. 2021 Sep;41(9):1345-1356. doi: 10.1002/jat.4124. Epub 2020 Nov 28.
Organophosphates (OPs) and pyrethroids (PYRs) are extensively used pesticides and often occur in the form of mixture, whereas little was known about their joint toxicities. We aim to investigate the individual and joint effects of OPs and PYRs exposure on zebrafish embryo by employing chlorpyrifos (CPF) and deltamethrin (DM) as representatives. Zebrafish embryos at 2 hours post fertilization (hpf) were exposed to CPF (4.80, 39.06, and 78.13 μg/L), DM exposure (0.06, 1.60, and 3.19 μg/L), and CPF + DM (4.80 + 0.06, 39.06 + 1.60, and 78.13 + 3.19 μg/L) until 144 hpf. Embryonic development, locomotor activity, and metabolomic changes were recorded and examined. Results displayed that individual exposure to CPF and DM significantly increased the mortality and malformation rate of zebrafish embryos, but decreased hatching rate was only found in CPF + DM co-exposure groups (p < .05). Meanwhile, individual CPF exposure had no detrimental effect on locomotor activity, high dose of individual CPF exposure decreased the swimming speed but had adaptability to the conversion from dark to light, whereas high dose of CPF + DM co-exposure exhibited not only significant decline in swimming speed but also no adaptability to the repeated stimulations, suggesting deficit in learning and memory function. In metabolomic analysis, individual CPF exposure mainly influenced the metabolism of glycerophospholipids and amino acids, individual DM exposure mainly influenced glycerophospholipids, and CPF + DM co-exposure mainly influenced glycerophospholipids and amino acids. Taken together, our findings suggested the embryonic toxicities and neurobehavioral changes caused by CPF and/or DM exposure. The disorder metabolomics of glycerophospholipids and amino acids might be involved in the underlying mechanism of those toxicities.
有机磷酸酯（OPs）和拟除虫菊酯（PYRs）是广泛使用的杀虫剂，且常以混合物形式出现，然而人们对它们的联合毒性知之甚少。我们旨在以毒死蜱（CPF）和溴氰菊酯（DM）为代表，研究OPs和PYRs暴露对斑马鱼胚胎的单独及联合影响。将受精后2小时（hpf）的斑马鱼胚胎暴露于CPF（4.80、39.06和78.13μg/L）、DM（0.06、1.60和3.19μg/L）以及CPF+DM（4.80+0.06、39.06+1.60和78.13+3.19μg/L）中，直至144 hpf。记录并检查胚胎发育、运动活性和代谢组学变化。结果显示，单独暴露于CPF和DM显著增加了斑马鱼胚胎的死亡率和畸形率，但仅在CPF+DM共同暴露组中发现孵化率降低（p<0.05）。同时，单独暴露于CPF对运动活性没有不利影响，高剂量单独暴露于CPF会降低游泳速度，但对从暗到光的转换具有适应性，而高剂量的CPF+DM共同暴露不仅显示游泳速度显著下降，而且对重复刺激没有适应性，表明学习和记忆功能存在缺陷。在代谢组学分析中，单独暴露于CPF主要影响甘油磷脂和氨基酸的代谢，单独暴露于DM主要影响甘油磷脂，而CPF+DM共同暴露主要影响甘油磷脂和氨基酸。综上所述，我们的研究结果表明CPF和/或DM暴露会导致胚胎毒性和神经行为变化。甘油磷脂和氨基酸的代谢组学紊乱可能参与了这些毒性的潜在机制。
