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

Citation
Sd. Pingree et al., Effects of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on tissue and urine mercury levels following prolonged methylmercury exposure in rats, TOXICOL SCI, 61(2), 2001, pp. 224-233
Citations number
30
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
10966080 → ACNP
Volume
61
Issue
2
Year of publication
2001
Pages
224 - 233
Database
ISI
SICI code
1096-6080(200106)61:2<224:EO2A(O>2.0.ZU;2-9
Abstract
Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimerc apto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to r educe brain, kidney, and blood Hg levels and to promote Hg elimination in u rine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg2+) and organic (CH3 Hg+) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS), Following MMH treatment for 9 weeks, Hg 2+ and CH3Hg+ concentrations were 0.28 and 4.80 mug/g in the brain and 51.5 and 42.2 mug/g in the kidney, respectively. Twenty-four hours after ip adm inistration of a single DMPS injection (100 mg/kg), kidney Hg2+ and CH3Hgdeclined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH3Hg+ fraction. Concomitantly, Hg2+ and CH3H g+ in urine increased by 7.2- and 28.3-fold, respectively, compared with pr echelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMP S injections (100 mg/kg) given at 72-h intervals significantly decreased to tal mercury concentrations in kidney, brain, and blood. However, the decrea se in brain and blood mercury content was restricted entirely to the CH3Hg fraction, consistent with the slow dealkylation rate of MMH in these tissu es. Mass balance calculations showed that the total amount of mercury excre ted in the urine following successive DMPS injections corresponds quantitat ively to the total amount of mercury removed from the kidney, brain, and bl ood 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 refle cts the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg2+ levels in b rain or blood may explain the inefficacy of DMPS and similar chelating agen ts in the remediation of neurotoxicity associated with prolonged MMH exposu re.