Heavy metal induced oxidative stress & its possible reversal by chelation therapy.
Heavy metal induced oxidative stress & its possible reversal by chelation therapy.
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发表时间：
2008-10
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通讯作者：
S. Flora;Megha Mittal;A. Mehta
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作者：
S. Flora;Megha Mittal;A. Mehta
由于重金属在环境中的普遍性，重金属暴露是一种普遍现象。金属中毒，特别是神经毒性、遗传毒性或致癌性是众所周知的。本文综述了近几年来有关类金属或重金属（特别是砷、铅、镉和汞）毒性作用的研究进展。确定所有这些金属的毒性和致癌性的统一因素是活性氧和氮物质的产生。这些金属的毒性表现主要是由于促氧化剂和抗氧化剂体内平衡之间的不平衡引起的，这被称为氧化应激。此外，这些金属对含有巯基的酶和蛋白质具有高亲和力，这些巯基负责正常的细胞防御机制。长期暴露于这些金属可能导致细胞凋亡。受金属影响的信号组分包括生长因子受体、G蛋白、MAP激酶和转录因子。螯合疗法使用螯合剂如乙二胺四乙酸二钠钙（CaNa（2）EDTA）、英国抗路易氏剂（BAL）、2，3-二巯基丙烷1-磺酸钠（DMPS）、内消旋2，3-二巯基琥珀酸（DMSA）等，被认为是对抗金属中毒的最好的治疗方法。尽管多年的研究，我们仍然远离有效的治疗，对毒性造成的接触重金属/类金属。这些螯合剂的治疗受到许多严重副作用的影响。研究表明，补充抗氧化剂与螯合剂证明是一个更好的治疗方案比单一的螯合剂。本文综述了重金属中毒研究的最新进展，特别是氧化应激/自由基在毒性表现中的作用，最近的螯合剂治疗策略的更新以及补充抗氧化剂以达到最佳效果的可能有益作用。我们只选择了砷，铅，汞和镉这篇文章保持在目前的关注和文献。
Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects. We have selected only arsenic, lead, mercury and cadmium for this article keeping in view current concerns and literature available.