Abstract:
Methyl mercury, a potent neurotoxicant, accumulates in the brain as well as kidney during chronic exposure. We evaluated the efficacy of DMPS, a tissue-permeable metal chelator, to reduce brain and kidney Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methyl mercury hydroxide MMH, (10 ppm) in drinking water for up to 9 weeks. The effects of DMPS on kidney and urinary porphyrin levels, a biomarker of renal Hg content and body burden, were also evaluated. Inorganic (Hg2+) and organic (CH3HG+) mercury species were assayed by CVAFS, whereas porphyrins were measured using HPLC. Prior to DMPS treatment, Hg2+ and CH3HG+ concentrations were 0.28 and 4.80mg/g in kidney, respectively. 24 hours after IP administration of a single DMPS injection (100mg/kg), kidney Hg2+ and CH3HG+ declined 38% and 59%, whereas brain mercury levels remained unchanged. Concomitantly, Hg2+ and CH3HG+ in urine increased by 7.2 and 28.3-fold, respectively. A higher dose of DMPS (200mg/kg) was as effective as 100mg/kg in promoting mercury excretion. However, consecutive DMPS injections were found to be highly effective at decreasing both Hg2+ and CH3HG+ mercury concentrations in the brain and kidney and increasing the mercury excreted in the urine. Kidney porphyrin concentrations were elevated nearly 4-fold in MMH-exposed rats, compared with unexposed controls. Following DMPS treatment, kidney coproporphyrin levels decreased by 1.5-fold, consistent with the depletion of renal Hg content. Urinary porphyrins were highly elevated following MMH exposure. After 3 consecutive DMPS injections the total urinary porphyrins declined to 19% of pre-chelation values. Lipid peroxidation and GSH levels in the tissue did not change following DMPS administration. These findings demonstrate the efficacy of DMPS in removal of both Hg2+ and CH3HG+ from brain and kidney. They also demonstrate a direct correlation between renal Hg and urinary porphyrin levels, confirming the efficacy of porphyrin measurements as biological marker of renal Hg accumulation and body burden.