AlexeyA.TINKOV, OlgaP.AJSUVAKOVA, JanAASETH, YordankaG.GLUHCHEVA, JulianaM.IVANOVA, GeirBJØRKLUND, MargaritaG.SKALNAYA, OksanaA.SKALNAYA, 黄百粲, 林雪, AnatolyV.SKALNY. 镉对生命活动的毒作用机制[J]. 环境与职业医学, 2018, 35(5): 460-470. DOI: 10.13213/j.cnki.jeom.2018.17516
引用本文: AlexeyA.TINKOV, OlgaP.AJSUVAKOVA, JanAASETH, YordankaG.GLUHCHEVA, JulianaM.IVANOVA, GeirBJØRKLUND, MargaritaG.SKALNAYA, OksanaA.SKALNAYA, 黄百粲, 林雪, AnatolyV.SKALNY. 镉对生命活动的毒作用机制[J]. 环境与职业医学, 2018, 35(5): 460-470. DOI: 10.13213/j.cnki.jeom.2018.17516
Alexey A. TINKOV, Olga P. AJSUVAKOVA, Jan AASETH, Yordanka G. GLUHCHEVA, Juliana M. IVANOVA, Geir BJØRKLUND, Margarita G. SKALNAYA, Oksana A. SKALNAYA, HUANG Pai-Tsang, LIN Xue, Anatoly V. SKALNY. Toxic mechanisms of cadmium on vital activities[J]. Journal of Environmental and Occupational Medicine, 2018, 35(5): 460-470. DOI: 10.13213/j.cnki.jeom.2018.17516
Citation: Alexey A. TINKOV, Olga P. AJSUVAKOVA, Jan AASETH, Yordanka G. GLUHCHEVA, Juliana M. IVANOVA, Geir BJØRKLUND, Margarita G. SKALNAYA, Oksana A. SKALNAYA, HUANG Pai-Tsang, LIN Xue, Anatoly V. SKALNY. Toxic mechanisms of cadmium on vital activities[J]. Journal of Environmental and Occupational Medicine, 2018, 35(5): 460-470. DOI: 10.13213/j.cnki.jeom.2018.17516
  • 摘要: 镉是一种众所周知的环境毒物,对人体健康有重大危害。镉与众多疾病相关,例如癌症、神经退化性疾病和代谢综合征等。虽然疾病种类各异,但是都与镉的化学性质和毒作用机制有关。镉易与含硫氮功能基结合,从而取代金属酶内的必需元素锌。镉的促炎症效应伴随促炎因子肿瘤坏死因子(TNF-α)、白介素(IL)-1、IL-6的大量产生和抗炎因子(IL-1拮抗剂、IL-4、IL-6、IL-10、IL-13)的明显减少,并且镉的促炎症活性与其通过各种途径所诱导的氧化应激紧密相关。镉还能取代各种蛋白质内的铁铜原子,从而增加自由氧化还原反应的活性金属库,激活芬顿(Fenton)反应;反之,镉对电子传递链的抑制损害了对氧气的利用,增加了活性氧的产生。最后,镉对抗氧化酶的抑制加剧自由基对核酸等生物大分子的损伤,引起遗传毒性并改变基因调控。因此,干扰镉的毒作用机制是预防镉暴露不良健康效应的有效措施。

     

    Abstract: Cadmium (Cd) is a well-known environmental toxicant posing significant health risks. In particular, Cd exposure is associated with numerous disorders including cancer, neurodegeneration, and metabolic syndrome. Despite the presence of multiple associated disorders, adverse health effects of the metal are mainly related to the universal mechanisms of toxicity that are tightly associated with Cd chemistry. Binding to sulfur- and nitrogen-containing functional groups, as well as the displacement of the essential element (zinc) from metalloenzymes, are considered as the primary mechanisms providing the basis for cadmium toxicity. Proinflammatory effect of Cd is associated with overproduction of proinflammatory cytokinestumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6) and a significant Cd-induced decrease in anti-inflammatory cytokine (IL-1 receptor antagonist, IL-4, IL-6, IL-10, IL-13) production. Proinflammatory activity of cadmium is tightly related to the induction of oxidative stress through various pathways. Cd is capable of replacement of iron and copper in various proteins resulting in increased free redox active metal pool and activation of Fenton chemistry. In turn, inhibition of the electron transport chain is associated with impaired oxygen handling and increased rate of reactive oxygen species production. Cd-induced inhibition of antioxidant enzymes aggravates free radical damage to macromolecules, including nucleic acids. The latter results in genotoxic effects of cadmium and subsequent altered gene regulation. Therefore, modulation of the mechanisms of Cd toxicity may be a useful measure for prevention of adverse health effects of Cd exposure.

     

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