Metal chelators and neurotoxicity: lead, mercury, and arsenic

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.