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首页> 外文期刊>Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems >Advances in metal-induced oxidative stress and human disease.
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Advances in metal-induced oxidative stress and human disease.

机译：金属诱导的氧化应激和人类疾病的研究进展。

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Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic activity to form ROS. A novel therapeutic approach to suppress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components. Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals. The aim of this review is to provide an overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals.
机译：过去二十年的详细研究表明，氧化还原活性金属（如铁（Fe），铜（Cu），铬（Cr），钴（Co）和其他金属）经历氧化还原循环反应，并具有产生反应性自由基的能力，例如生物系统中的超氧阴离子自由基和一氧化氮。金属离子稳态的破坏可能会导致氧化应激，这种状态下活性氧（ROS）形成的增加使身体的抗氧化保护不堪重负，并随后诱发DNA损伤，脂质过氧化，蛋白质修饰和其他作用，所有这些症状均涉及多种疾病，包括癌症，心血管疾病，糖尿病，动脉粥样硬化，神经系统疾病（阿尔茨海默氏病，帕金森氏病），慢性炎症等。所有这些金属的基本作用机理涉及超氧化物自由基，羟基自由基（主要通过芬顿反应）和其他ROS的形成，最终产生诱变和致癌的丙二醛（MDA），4-羟基壬烯（HNE）和其他环外DNA加合物。另一方面，氧化还原惰性金属，例如镉（Cd），砷（As）和铅（Pb）通过与蛋白质的硫代基团结合和消耗谷胱甘肽而显示出毒性作用。有趣的是，对于砷，已经提出了在生理条件下基于过氧化氢形成的另一种作用机理。金属间的特殊位置是氧化还原惰性金属锌（Zn）。锌是参与抗氧化应激的众多蛋白质的重要​​成分。已经表明，锌的消耗可通过DNA修复机制的损伤而增强DNA损伤。另外，锌对免疫系统有影响，并具有神经保护特性。金属诱导的自由基形成机理受到细胞抗氧化剂作用的严格影响。许多低分子量抗氧化剂（抗坏血酸（维生素C），α-生育酚（维生素E），谷胱甘肽（GSH），类胡萝卜素，类黄酮和其他抗氧化剂）能够螯合金属离子，从而降低其催化活性，从而形成ROS。一种抑制氧化应激的新型治疗方法是基于双功能抗氧化剂的开发，该抗氧化剂不仅包含螯合成分，还包含清除成分。矛盾的是，两种主要的抗氧化酶，即超氧化物歧化酶（SOD）和过氧化氢酶，其活性位点中都含有金属离子，以对抗金属诱导的自由基的毒性作用。这篇综述的目的是概述氧化还原和非氧化还原金属诱导的自由基的形成以及氧化应激在金属毒性作用中的作用。

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