Chen Shen , Zhi-Guo Sheng , Jie Shao , Miao Tang , Li Mao , Chun-Hua Huang , Zhi-Hui Zhang , Ben-Zhan Zhu
{"title":"农药元钠与铜或锌差异协同神经毒性的机理研究","authors":"Chen Shen , Zhi-Guo Sheng , Jie Shao , Miao Tang , Li Mao , Chun-Hua Huang , Zhi-Hui Zhang , Ben-Zhan Zhu","doi":"10.1016/j.chemosphere.2023.138430","DOIUrl":null,"url":null,"abstract":"<div><p>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<sup>2+</sup>) or zinc ion (Zn<sup>2+</sup>) is able to cause synergistic neurotoxicity in neural PC12 cells and its possible mechanism(s). We found that both metam/Cu<sup>2+</sup> and metam/Zn<sup>2+</sup> synergistically induced apoptosis, intracellular Cu<sup>2+</sup>/Zn<sup>2+</sup><span> uptake, reactive oxygen species (ROS) accumulation, double-strand DNA breakage, mitochondrial membrane potential decrease, and nerve function disorder. In addition, metam/Cu</span><sup>2+</sup><span> was shown to release cytochrome </span><em>c</em> and apoptosis-inducing factor (AIF) from mitochondria to cytoplasm and nucleus, respectively, and activate the caspase 9, 8, 3, 7. However, metam/Zn<sup>2+</sup> induced caspase 7 activation and AIF translocation and mildly activated cytochrome <em>c</em>/caspase 9/caspase 3 pathway. Furthermore, metam/Cu<sup>2+</sup> activated caspase 3/7 by the p38 pathway, whereas metam/Zn<sup>2+</sup> did so via both the p38 and JNK pathways. These results demonstrated that metam/Cu<sup>2+</sup> or metam/Zn<sup>2+</sup> co-exposure cause synergistic neurotoxicity via different mechanisms, indicating a potential risk to human health when they environmentally co-exist.</p></div>","PeriodicalId":276,"journal":{"name":"Chemosphere","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanistic investigation of the differential synergistic neurotoxicity between pesticide metam sodium and copper or zinc\",\"authors\":\"Chen Shen , Zhi-Guo Sheng , Jie Shao , Miao Tang , Li Mao , Chun-Hua Huang , Zhi-Hui Zhang , Ben-Zhan Zhu\",\"doi\":\"10.1016/j.chemosphere.2023.138430\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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<sup>2+</sup>) or zinc ion (Zn<sup>2+</sup>) is able to cause synergistic neurotoxicity in neural PC12 cells and its possible mechanism(s). We found that both metam/Cu<sup>2+</sup> and metam/Zn<sup>2+</sup> synergistically induced apoptosis, intracellular Cu<sup>2+</sup>/Zn<sup>2+</sup><span> uptake, reactive oxygen species (ROS) accumulation, double-strand DNA breakage, mitochondrial membrane potential decrease, and nerve function disorder. In addition, metam/Cu</span><sup>2+</sup><span> was shown to release cytochrome </span><em>c</em> and apoptosis-inducing factor (AIF) from mitochondria to cytoplasm and nucleus, respectively, and activate the caspase 9, 8, 3, 7. However, metam/Zn<sup>2+</sup> induced caspase 7 activation and AIF translocation and mildly activated cytochrome <em>c</em>/caspase 9/caspase 3 pathway. Furthermore, metam/Cu<sup>2+</sup> activated caspase 3/7 by the p38 pathway, whereas metam/Zn<sup>2+</sup> did so via both the p38 and JNK pathways. These results demonstrated that metam/Cu<sup>2+</sup> or metam/Zn<sup>2+</sup> co-exposure cause synergistic neurotoxicity via different mechanisms, indicating a potential risk to human health when they environmentally co-exist.</p></div>\",\"PeriodicalId\":276,\"journal\":{\"name\":\"Chemosphere\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemosphere\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0045653523006975\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemosphere","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045653523006975","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Mechanistic investigation of the differential synergistic neurotoxicity between pesticide metam sodium and copper or zinc
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 (Cu2+) or zinc ion (Zn2+) is able to cause synergistic neurotoxicity in neural PC12 cells and its possible mechanism(s). We found that both metam/Cu2+ and metam/Zn2+ synergistically induced apoptosis, intracellular Cu2+/Zn2+ uptake, reactive oxygen species (ROS) accumulation, double-strand DNA breakage, mitochondrial membrane potential decrease, and nerve function disorder. In addition, metam/Cu2+ 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/Zn2+ induced caspase 7 activation and AIF translocation and mildly activated cytochrome c/caspase 9/caspase 3 pathway. Furthermore, metam/Cu2+ activated caspase 3/7 by the p38 pathway, whereas metam/Zn2+ did so via both the p38 and JNK pathways. These results demonstrated that metam/Cu2+ or metam/Zn2+ co-exposure cause synergistic neurotoxicity via different mechanisms, indicating a potential risk to human health when they environmentally co-exist.
期刊介绍:
Chemosphere, being an international multidisciplinary journal, is dedicated to publishing original communications and review articles on chemicals in the environment. The scope covers a wide range of topics, including the identification, quantification, behavior, fate, toxicology, treatment, and remediation of chemicals in the bio-, hydro-, litho-, and atmosphere, ensuring the broad dissemination of research in this field.