Corradi Massimo, Mutti Antonio
Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, I-43100 Parma, Italy.
Met Ions Life Sci. 2011;8:81-105.
Some metals, such as copper and manganese, are essential to life and play irreplaceable roles in, e.g., the functioning of important enzyme systems. Other metals are xenobiotics, i.e., they have no useful role in human physiology and, even worse, as in the case of lead, may be toxic even at trace levels of exposure. Even those metals that are essential, however, have the potential to turn harmful at very high levels of exposure, a reflection of a very basic tenet of toxicology--"the dose makes the poison." Toxic metal exposure may lead to serious risks to human health. As a result of the extensive use of toxic metals and their compounds in industry and consumer products, these agents have been widely disseminated in the environment. Because metals are not biodegradable, they can persist in the environment and produce a variety of adverse effects. Exposure to metals can lead to damage in a variety of organ systems and, in some cases, metals also have the potential to be carcinogenic. Even though the importance of metals as environmental health hazards is now widely appreciated, the specific mechanisms by which metals produce their adverse effects have yet to be fully elucidated. The unifying factor in determining toxicity and carcinogenicity for most metals is the generation of reactive oxygen and nitrogen species. Metal-mediated formation of free radicals causes various modifications to nucleic acids, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Whilst copper, chromium, and cobalt undergo redox-cycling reactions, for metals such as cadmium and nickel the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. This chapter attempts to show that the toxic effects of different metallic compounds may be manifested in the pulmonary and cardiovascular systems. The knowledge of health effects due to metal exposure is necessary for practising physicians, and should be assessed by inquiring about present and past occupational history and environmental exposure.
一些金属，如铜和锰，是生命所必需的，在重要酶系统的功能等方面发挥着不可替代的作用。其他金属则是外源性物质，即它们在人体生理中没有有益作用，甚至更糟的是，如铅的情况，即使在微量接触水平下也可能有毒。然而，即使是那些必需的金属，在极高的接触水平下也有可能变得有害，这反映了毒理学的一个非常基本的原则——“剂量决定毒性”。有毒金属暴露可能对人类健康造成严重风险。由于有毒金属及其化合物在工业和消费品中的广泛使用，这些物质已在环境中广泛传播。因为金属是不可生物降解的，它们可以在环境中持续存在并产生各种不利影响。接触金属会导致多种器官系统受损，在某些情况下，金属还具有致癌潜力。尽管金属作为环境健康危害的重要性现在已得到广泛认可，但金属产生不利影响的具体机制尚未完全阐明。大多数金属毒性和致癌性的统一决定因素是活性氧和氮物种的产生。金属介导的自由基形成会对核酸造成各种修饰，增强脂质过氧化，并改变钙和巯基的稳态。虽然铜、铬和钴会发生氧化还原循环反应，但对于镉和镍等金属来说，其毒性的主要途径是谷胱甘肽的消耗以及与蛋白质的巯基结合。本章试图表明，不同金属化合物的毒性作用可能在肺部和心血管系统中表现出来。执业医生必须了解金属暴露对健康的影响，应通过询问当前和过去的职业史及环境暴露情况来进行评估。
