Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway.
Paracelsus Clinica al Ronc, Castaneda, Switzerland.
Arch Toxicol. 2017 Dec;91(12):3787-3797. doi: 10.1007/s00204-017-2100-0. Epub 2017 Oct 24.
This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.
本文综述了金属螯合剂 2,3-二巯基-1-丙磺酸（DMPS）、meso-2,3-二巯基丁二酸（DMSA）和依地酸二钠钙（CaEDTA，钙 EDTA）在铅（Pb）、汞（Hg）和砷（As）盐过量暴露和中毒中的临床应用。DMSA 的毒性明显低于经典重金属拮抗剂 BAL（2,3-二巯基丙醇），毒性也低于 DMPS。由于其不良反应，在治疗中度 Pb 中毒时，应将 CaEDTA 用 DMSA 取代为首选解毒剂。以前曾建议在伴有脑病的严重急性 Pb 中毒的情况下联合使用 BAL 和 CaEDTA 进行治疗。我们建议在这种情况下，BAL 作为一种穿梭 Pb 转运蛋白，将 Pb 从细胞内转运到细胞外。本文讨论了将细胞外分布的 DMSA 与离子载体 Monensin 联合使用是否可以通过增加细胞内沉积的 Pb 的流出和尿 Pb 排泄来提供一种毒性更小的 Pb 动员组合。无论如何，应继续使用几个间歇性疗程进行 DMSA 的口服治疗。DMPS 和 DMSA 也是 Hg 中毒的有前途的解毒剂，而 DMPS 似乎对 As 中毒更有效。然而，新的见解表明，低剂量 BAL 加 DMPS 的联合治疗可能是首选的解毒治疗方法，以将脑内沉积的 Pb 动员到循环中，随后迅速通过尿液排出。
