Ercal N, Gurer-Orhan H, Aykin-Burns N
University of Missouri-Rolla, Department of Chemistry, 65409-0010, USA.
Curr Top Med Chem. 2001 Dec;1(6):529-39. doi: 10.2174/1568026013394831.
Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals. In order to prove the importance of using antioxidants in heavy metal poisoning, pertinent biochemical mechanisms for metal-induced oxidative stress should be reviewed.
有毒金属（铅、镉、汞和砷）在我们的环境中广泛存在。人类通过多种途径接触到这些金属，包括受污染的空气、水、土壤和食物。最近的研究表明，过渡金属在生物大分子的氧化反应中起催化剂作用，因此与这些金属相关的毒性可能是由于氧化组织损伤。具有氧化还原活性的金属，如铁、铜和铬，会进行氧化还原循环，而无氧化还原活性的金属，如铅、镉、汞等，则会消耗细胞中的主要抗氧化剂，特别是含硫醇的抗氧化剂和酶。无论是具有氧化还原活性的金属还是无氧化还原活性的金属，都可能导致活性氧（ROS）如羟基自由基（HO·）、超氧阴离子自由基（O2-·）或过氧化氢（H2O2）的产生增加。ROS生成的增强会使细胞固有的抗氧化防御能力不堪重负，从而导致一种称为“氧化应激”的状态。处于氧化应激状态的细胞由于ROS对脂质、蛋白质和DNA造成的损伤而表现出各种功能障碍。因此，有人认为细胞中金属诱导的氧化应激可能部分导致了重金属的毒性作用。目前正在进行多项研究以确定重金属暴露后补充抗氧化剂的效果。数据表明，抗氧化剂可能在减轻重金属的某些危害方面发挥重要作用。为了证明在重金属中毒中使用抗氧化剂的重要性，应该回顾金属诱导氧化应激的相关生化机制。
