State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Chemosphere. 2023 Jul;328:138430. doi: 10.1016/j.chemosphere.2023.138430. Epub 2023 Mar 22.
Epidemiological studies suggest neurological disorders have been associated with the co-exposure to certain pesticides and transition metals. The present study aims to investigate whether co-exposure to the widely-used pesticide metam sodium and copper (Cu) or zinc ion (Zn) is able to cause synergistic neurotoxicity in neural PC12 cells and its possible mechanism(s). We found that both metam/Cu and metam/Zn synergistically induced apoptosis, intracellular Cu/Zn uptake, reactive oxygen species (ROS) accumulation, double-strand DNA breakage, mitochondrial membrane potential decrease, and nerve function disorder. In addition, metam/Cu was shown to release cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to cytoplasm and nucleus, respectively, and activate the caspase 9, 8, 3, 7. However, metam/Zn induced caspase 7 activation and AIF translocation and mildly activated cytochrome c/caspase 9/caspase 3 pathway. Furthermore, metam/Cu activated caspase 3/7 by the p38 pathway, whereas metam/Zn did so via both the p38 and JNK pathways. These results demonstrated that metam/Cu or metam/Zn co-exposure cause synergistic neurotoxicity via different mechanisms, indicating a potential risk to human health when they environmentally co-exist.
流行病学研究表明，神经系统疾病与某些杀虫剂和过渡金属的共同暴露有关。本研究旨在探讨广泛使用的杀虫剂甲拌磷与铜（Cu）或锌离子（Zn）共同暴露是否会导致神经 PC12 细胞产生协同神经毒性及其可能的机制。我们发现，甲拌磷/Cu 和甲拌磷/Zn 均协同诱导细胞凋亡、细胞内 Cu/Zn 摄取、活性氧（ROS）积累、双链 DNA 断裂、线粒体膜电位下降和神经功能障碍。此外，甲拌磷/Cu 被证明将细胞色素 c 和凋亡诱导因子（AIF）分别从线粒体释放到细胞质和细胞核，并激活半胱天冬酶 9、8、3、7。然而，甲拌磷/Zn 仅轻度激活细胞色素 c/半胱天冬酶 9/半胱天冬酶 3 途径，诱导半胱天冬酶 7 激活和 AIF 易位。此外，甲拌磷/Cu 通过 p38 途径激活半胱天冬酶 3/7，而甲拌磷/Zn 则通过 p38 和 JNK 途径激活。这些结果表明，甲拌磷/Cu 或甲拌磷/Zn 共同暴露通过不同的机制导致协同神经毒性，表明当它们在环境中共存时，可能对人类健康构成潜在风险。
