{"title":"利用大鼠神经元皮层培养研究锂诱导的神经毒性的新方法:氧化应激和溶酶体/线粒体毒性串扰的参与","authors":"B. Yousefsani, R. Askian, J. Pourahmad","doi":"10.1515/mgmc-2020-0003","DOIUrl":null,"url":null,"abstract":"Abstract Lithium (Li) is a widely-used medication for the treatment of patients with bipolar disorder. Li causes different complications. One of the most important adverse effects of Li is neurotoxicity. Neurotoxicity is usually irreversible which may lead to very important complications. The symptoms of Li-induced neurotoxicity include tremor, delirium, seizures, coma, and death. In this study, we wanted to evaluate the exact sub-cellular mechanisms of Li-induced neurotoxicity. For this purpose, we used primary neuronal cortical culture for investigating lithium-induced neurotoxicity. We applied the postnatal rat pups for isolating the cortical neurons. After that, we evaluated neural viability, neural reactive oxygen specious (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), lysosomal membrane integrity (LMI), and reduced (GSH) and oxidized (GSSG) glutathione. Our results demonstrated that the cytotoxic effect of Li has mediated through lysosomal membrane leakage associated with ROS formation and reduction of MMP. Furthermore, the incubation of isolated neurons with Li caused rapid GSH depletion (as GSSG efflux) as another marker of cellular oxidative stress. We concluded that Li causes neurotoxicity in a dose-dependent manner. Besides, Li-induced neurotoxicity is a result of the generation of ROS and LP, which leads to mitochondrial/lysosomal toxic cross-talk.","PeriodicalId":48891,"journal":{"name":"Main Group Metal Chemistry","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/mgmc-2020-0003","citationCount":"4","resultStr":"{\"title\":\"A new approach on lithium-induced neurotoxicity using rat neuronal cortical culture: Involvement of oxidative stress and lysosomal/mitochondrial toxic Cross-Talk\",\"authors\":\"B. Yousefsani, R. Askian, J. Pourahmad\",\"doi\":\"10.1515/mgmc-2020-0003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Abstract Lithium (Li) is a widely-used medication for the treatment of patients with bipolar disorder. Li causes different complications. One of the most important adverse effects of Li is neurotoxicity. Neurotoxicity is usually irreversible which may lead to very important complications. The symptoms of Li-induced neurotoxicity include tremor, delirium, seizures, coma, and death. In this study, we wanted to evaluate the exact sub-cellular mechanisms of Li-induced neurotoxicity. For this purpose, we used primary neuronal cortical culture for investigating lithium-induced neurotoxicity. We applied the postnatal rat pups for isolating the cortical neurons. After that, we evaluated neural viability, neural reactive oxygen specious (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), lysosomal membrane integrity (LMI), and reduced (GSH) and oxidized (GSSG) glutathione. Our results demonstrated that the cytotoxic effect of Li has mediated through lysosomal membrane leakage associated with ROS formation and reduction of MMP. Furthermore, the incubation of isolated neurons with Li caused rapid GSH depletion (as GSSG efflux) as another marker of cellular oxidative stress. We concluded that Li causes neurotoxicity in a dose-dependent manner. Besides, Li-induced neurotoxicity is a result of the generation of ROS and LP, which leads to mitochondrial/lysosomal toxic cross-talk.\",\"PeriodicalId\":48891,\"journal\":{\"name\":\"Main Group Metal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1515/mgmc-2020-0003\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Main Group Metal Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1515/mgmc-2020-0003\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Main Group Metal Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1515/mgmc-2020-0003","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
A new approach on lithium-induced neurotoxicity using rat neuronal cortical culture: Involvement of oxidative stress and lysosomal/mitochondrial toxic Cross-Talk
Abstract Lithium (Li) is a widely-used medication for the treatment of patients with bipolar disorder. Li causes different complications. One of the most important adverse effects of Li is neurotoxicity. Neurotoxicity is usually irreversible which may lead to very important complications. The symptoms of Li-induced neurotoxicity include tremor, delirium, seizures, coma, and death. In this study, we wanted to evaluate the exact sub-cellular mechanisms of Li-induced neurotoxicity. For this purpose, we used primary neuronal cortical culture for investigating lithium-induced neurotoxicity. We applied the postnatal rat pups for isolating the cortical neurons. After that, we evaluated neural viability, neural reactive oxygen specious (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), lysosomal membrane integrity (LMI), and reduced (GSH) and oxidized (GSSG) glutathione. Our results demonstrated that the cytotoxic effect of Li has mediated through lysosomal membrane leakage associated with ROS formation and reduction of MMP. Furthermore, the incubation of isolated neurons with Li caused rapid GSH depletion (as GSSG efflux) as another marker of cellular oxidative stress. We concluded that Li causes neurotoxicity in a dose-dependent manner. Besides, Li-induced neurotoxicity is a result of the generation of ROS and LP, which leads to mitochondrial/lysosomal toxic cross-talk.
期刊介绍:
This journal is committed to the publication of short communications, original research, and review articles within the field of main group metal and semi-metal chemistry, Main Group Metal Chemistry is an open-access, peer-reviewed journal that publishes in ongoing way. Papers addressing the theoretical, spectroscopic, mechanistic and synthetic aspects of inorganic, coordination and organometallic main group metal and semi-metal compounds, including zinc, cadmium and mercury are welcome. The journal also publishes studies relating to environmental aspects of these metals, their toxicology, release pathways and fate. Articles on the applications of main group metal chemistry, including in the fields of polymer chemistry, agriculture, electronics and catalysis, are also accepted.