Evaluation of the potential role of chelation therapy in treatment of low to moderate lead exposures.

Abstract

In the overall long-term management of lead poisoning, chelation therapy can have short-term benefits; however, these benefits must be accompanied by drastic reduction in environmental exposure to lead if therapy is to have any long-term benefit. This discussion is limited to calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), the chelating agent that has been the mainstay of treatment of lead poisoning for the past 38 years, and to meso-2,3-dimercaptosuccinic acid (DMSA), a new and promising oral chelating agent, which is an orphan drug and is currently classified as an investigational new drug by the U.S. Food and Drug Administration. With both drugs, multiple courses of treatment will be needed if any substantial reduction in body lead burden is to be achieved. A major limitation of CaNa2EDTA is the enormous diuresis of zinc that it produces. DMSA produces a comparable diuresis of lead, a greater decrease in blood lead, and has negligible influence on the urinary losses of zinc, copper, iron, and calcium. Limited experience to date in man has revealed no significant adverse side effects of DMSA. In animals, DMSA will promptly reduce the concentration of lead in brain and kidney, in particular. By contrast, similar 5-day courses of CaNa2EDTA do not produce any net reduction in brain lead. This is important, as the brain is the critical organ of the adverse effects of lead in children. If the efficacy of DMSA is to be comprehensively evaluated ethically in children, new and more sensitive neurochemical, electrophysiologic, or other markers must be developed.

Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites.

“…Notably, the two and four hour cumulative lead excretions after DMSA correlated highly with the eight hour total in the 34 subjects (r = 0-76 for two hour v eight hour and r = 0 95 for four hour v eight hour), which suggests that a two or four hour urine collection would be adequate to estimate DMSA-chelatable lead. The eight hour cumulative lead excretions after DMSA and EDTA showed a modest correlation (r = 20 25 0 44, P = 0-08, n = 17); this value increased to r = 0-83 (P < 0-001) after the removal of two outliers. One of these subjects, who had DMSA first, had an eight hour lead excretion DMSA v of 4417 ug after EDTA but only 768 pg after i baseline DMSA.…”

Mechanisms of lead and manganese neurotoxicity

“…The developing world, with increased toxic metal contamination and higher prevalence of dietary deficiencies, is at particular risk for metal toxicity. The demonstrated irreversible nature of the effects of Pb 91–93 on neurodevelopment, and the potential for the same with Mn, 237 strongly supports environmental intervention in regions where children are exposed to these metals via polluted air or ground water.…”

“…91–93 Prenatal and/or childhood Pb exposure was associated with anti-social and delinquent behaviour as adolescents, 94 an increased likelihood be an adjudicated delinquent 95 or to be arrested as an adult. 96 Furthermore, childhood Pb exposure may predict adult cognitive function.…”

Mechanisms of Heavy Metal Neurotoxicity: Lead and Manganese

“…The cognitive and behavioral deficits of Pb 2+ -exposed children persist even after the cessation of Pb 2+ exposure [87], and chelation therapy is unable to remediate the effect of Pb 2+ on cognition [88][89][90]. Prenatal and/or childhood Pb 2+ exposure was associated with anti-social and delinquent behavior as adolescents [91], an increased likelihood be an adjudicated delinquent [92] or to be arrested as an adult [93].…”