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

IF 1.8 3区 化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Main Group Metal Chemistry Pub Date : 2020-01-01 DOI:10.1515/mgmc-2020-0003
B. Yousefsani, R. Askian, J. Pourahmad
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引用次数: 4

摘要

锂(Li)是一种广泛用于治疗双相情感障碍患者的药物。李引起不同的并发症。Li最重要的副作用之一是神经毒性。神经毒性通常是不可逆的,可能导致非常严重的并发症。锂诱发的神经毒性症状包括震颤、谵妄、癫痫发作、昏迷和死亡。在这项研究中,我们想要评估锂诱导的神经毒性的确切亚细胞机制。为此,我们使用原代神经元皮层培养来研究锂诱导的神经毒性。我们用出生后的大鼠幼鼠分离皮质神经元。之后,我们评估了神经活力、神经活性氧(ROS)、脂质过氧化、线粒体膜电位(MMP)、溶酶体膜完整性(LMI)和还原性(GSH)和氧化性(GSSG)谷胱甘肽。我们的研究结果表明,Li的细胞毒性作用是通过与ROS形成和MMP减少相关的溶酶体膜渗漏介导的。此外,与Li一起培养的离体神经元引起GSH快速耗竭(作为GSSG外排),这是细胞氧化应激的另一个标志。我们得出结论,Li以剂量依赖的方式引起神经毒性。此外,锂诱导的神经毒性是由于ROS和LP的产生,导致线粒体/溶酶体毒性串扰。
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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.
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来源期刊
Main Group Metal Chemistry
Main Group Metal Chemistry CHEMISTRY, INORGANIC & NUCLEAR-CHEMISTRY, ORGANIC
CiteScore
4.10
自引率
27.80%
发文量
21
审稿时长
4 weeks
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.
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