Stohs S J, Bagchi D
School of Pharmacy, Creighton University, Omaha, NE 68178, USA.
Free Radic Biol Med. 1995 Feb;18(2):321-36. doi: 10.1016/0891-5849(94)00159-h.
The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.
本文综述了活性氧在与过渡金属离子相关毒性中致使生物大分子发生氧化降解的作用。近期研究表明，包括铁、铜、铬和钒在内的金属会经历氧化还原循环，而镉、汞、镍以及铅会消耗谷胱甘肽和蛋白质结合的巯基，从而产生超氧离子、过氧化氢和羟基自由基等活性氧。结果导致脂质过氧化增强、DNA损伤以及钙和巯基稳态改变。类芬顿反应可能普遍与包括线粒体、微粒体和过氧化物酶体在内的大多数膜性组分相关。吞噬细胞可能是响应金属离子时活性氧的另一个重要来源。此外，各种研究表明，通过氧化还原循环醌类及相关化合物产生活性氧的能力可能需要金属离子。近期研究表明，金属离子可能会增强肿瘤坏死因子α（TNFα）的产生并激活蛋白激酶C，以及诱导应激蛋白的产生。因此，一些与金属离子毒性相关的机制与许多有机外源化合物产生的效应非常相似。金属离子毒性的具体差异可能与溶解度、吸收性、转运、化学反应性以及体内形成的复合物的差异有关。本文综述了目前关于过渡金属离子以及铅在活性氧产生和氧化组织损伤方面的研究。
