Sears Margaret E
Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, Canada.
ScientificWorldJournal. 2013 Apr 18;2013:219840. doi: 10.1155/2013/219840. Print 2013.
Toxic metals such as arsenic, cadmium, lead, and mercury are ubiquitous, have no beneficial role in human homeostasis, and contribute to noncommunicable chronic diseases. While novel drug targets for chronic disease are eagerly sought, potentially helpful agents that aid in detoxification of toxic elements, chelators, have largely been restricted to overt acute poisoning. Chelation, that is multiple coordination bonds between organic molecules and metals, is very common in the body and at the heart of enzymes with a metal cofactor such as copper or zinc. Peptides glutathione and metallothionein chelate both essential and toxic elements as they are sequestered, transported, and excreted. Enhancing natural chelation detoxification pathways, as well as use of pharmaceutical chelators against heavy metals are reviewed. Historical adverse outcomes with chelators, lessons learned in the art of using them, and successes using chelation to ameliorate renal, cardiovascular, and neurological conditions highlight the need for renewed attention to simple, safe, inexpensive interventions that offer potential to stem the tide of debilitating, expensive chronic disease.
砷、镉、铅和汞等有毒金属无处不在,在人体稳态中没有有益作用,还会导致非传染性慢性病。虽然人们急切地寻找慢性病的新型药物靶点,但有助于有毒元素解毒的潜在有用药物——螯合剂,在很大程度上仅限于明显的急性中毒情况。螯合作用,即有机分子与金属之间的多重配位键,在体内非常普遍,并且是具有金属辅因子(如铜或锌)的酶的核心。肽谷胱甘肽和金属硫蛋白在元素被隔离、运输和排泄时螯合必需元素和有毒元素。本文综述了增强天然螯合解毒途径以及使用针对重金属的药物螯合剂的情况。螯合剂的历史不良后果、使用它们的经验教训,以及使用螯合作用改善肾脏、心血管和神经疾病的成功案例,都凸显了需要重新关注简单、安全、廉价的干预措施,这些措施有可能阻止使人衰弱且昂贵的慢性病的蔓延趋势。