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毒死蜱和镉对神经细胞氧化应激及线粒体损伤的联合毒性

Joint toxicity of chlorpyrifos and cadmium on the oxidative stress and mitochondrial damage in neuronal cells.

作者信息

Xu Ming-Yuan, Wang Pan, Sun Ying-Jian, Yang Lin, Wu Yi-Jun

机构信息

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.

Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.

出版信息

Food Chem Toxicol. 2017 May;103:246-252. doi: 10.1016/j.fct.2017.03.013. Epub 2017 Mar 9.

Abstract

Pesticides and heavy metals can be easily biomagnified in food chains and bioaccumulated in individuals, thus pose significant threat to human health. However, their joint toxicity for long-term exposure at low dose has not been thoroughly investigated. In the present study, we investigated the oxidative damages in brain of rats exposed subchronically to organophosphorus pesticide chlorpyrifos (CPF) and heavy metal cadmium (Cd), and their mixtures at the environmentally relevant doses. Rats were given different doses of CPF and Cd by oral gavage for three months. After treatment, brain tissues were subjected for biochemical analysis. Mitochondrial damage and reactive oxidative species were also measured in neuroblastoma SH-SY5Y cells treated with CPF, Cd and their mixtures. The results showed that CPF and Cd generated protein and lipid peroxidation, disturbed the total antioxidant capability, and altered mitochondria ultrastructure in the brain. Lipids and proteins were sensitive to the oxidative damage induced by CPF and Cd. CPF and Cd decreased mitochondrial potential and induced reactive oxygen species in SH-SY5Y cells. However, the mixture did not display higher toxicity than the sum of that of the individual treatments. Thus, CPF and Cd could have a potential antagonistic interaction on the induction of oxidative stress.

摘要

农药和重金属很容易在食物链中生物放大,并在个体中生物累积,从而对人类健康构成重大威胁。然而,它们在低剂量长期暴露下的联合毒性尚未得到充分研究。在本研究中,我们调查了亚慢性暴露于有机磷农药毒死蜱(CPF)和重金属镉(Cd)及其环境相关剂量混合物的大鼠大脑中的氧化损伤。通过口服灌胃给予大鼠不同剂量的CPF和Cd,持续三个月。处理后,对脑组织进行生化分析。还用CPF、Cd及其混合物处理神经母细胞瘤SH-SY5Y细胞,测定线粒体损伤和活性氧化物质。结果表明,CPF和Cd导致蛋白质和脂质过氧化,扰乱总抗氧化能力,并改变大脑中的线粒体超微结构。脂质和蛋白质对CPF和Cd诱导的氧化损伤敏感。CPF和Cd降低了SH-SY5Y细胞中的线粒体电位并诱导活性氧产生。然而,混合物并未表现出比单独处理的总和更高的毒性。因此,CPF和Cd在诱导氧化应激方面可能存在潜在的拮抗作用。

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