Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on tissue and urine mercury levels following prolonged methylmercury exposure in rats.

Abstract

Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to reduce brain, kidney, and blood Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg²⁺) and organic (CH₃Hg⁺) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS). Following MMH treatment for 9 weeks, Hg²⁺ and CH₃Hg⁺ concentrations were 0.28 and 4.80 μg/g in the brain and 51.5 and 42.2 μg/g in the kidney, respectively. Twenty-four hours after ip administration of a single DMPS injection (100 mg/kg), kidney Hg²⁺ and CH₃Hg⁺ declined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH₃Hg⁺ fraction. Concomitantly, Hg²⁺ and CH₃Hg⁺ in urine increased by 7.2- and 28.3-fold, respectively, compared with prechelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMPS injections (100 mg/kg) given at 72-h intervals significantly decreased total mercury concentrations in kidney, brain, and blood. However, the decrease in brain and blood mercury content was restricted entirely to the CH₃Hg⁺ fraction, consistent with the slow dealkylation rate of MMH in these tissues. Mass balance calculations showed that the total amount of mercury excreted in the urine following successive DMPS injections corresponds quantitatively to the total amount of mercury removed from the kidney, brain, and blood of MMH-exposed rats. These findings confirm the efficacy of consecutive DMPS treatments in decreasing mercury concentrations in target tissue and in reducing overall mercury body burden. They demonstrate further that the capacity of DMPS to deplete tissue Hg²⁺ is highly tissue-specific and reflects the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg²⁺ levels in brain or blood may explain the inefficacy of DMPS and similar chelating agents in the remediation of neurotoxicity associated with prolonged MMH exposure.