Council for Nutritional and Environmental Medicine, N-8610 Mo i Rana, Norway.
Cittadella Universitaria, University of Cagliari, 09042 Cagliari, Italy.
Molecules. 2019 Sep 6;24(18):3247. doi: 10.3390/molecules24183247.
The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg, Cd, and Pb are reviewed since insight into these reactions can provide a basis for further development of therapeutics.
本文综述了巯基类金属螯合剂在汞(Hg)、镉(Cd)和铅(Pb)中毒和过量暴露中的临床应用。目前,只有极少数商业上可用的药物可以成功减轻或预防这些金属的毒性。金属螯合剂 meso-2,3-二巯基丁二酸(DMSA)的毒性明显低于经典药物二巯丁二钠(BAL,2,3-二巯基丙醇),是治疗 Pb 和有机 Hg 中毒的推荐药物。其毒性也低于 DMPS(二巯丙磺酸钠),尽管 DMPS 是治疗 Hg 盐急性中毒的推荐药物。据认为,解毒剂的联合应用可以在一定程度上动员细胞内的 Cd 沉积和无机 Hg 的脑内沉积,但缺乏此类联合应用的临床经验。α-硫辛酸(α-LA)已被提议用于解毒毒性金属,但在临床实践中并不被认为是首选药物。综述了螯合剂与 Hg、Cd 和 Pb 金属离子形成配合物的分子机制和化学平衡,因为对这些反应的深入了解可以为治疗学的进一步发展提供基础。