Influence of 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of mercury in normal and uninephrectomized rats exposed to inorganic mercury.
The effects of the water-soluble chelating agents 2,3-dimercapto-1-propane sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of inorganic mercury were studied in normal and uninephrectomized (NPX) rats injected (i.v.) with a nontoxic 0.5-mumol/kg dose of mercuric chloride (HgCl2). When a 100-mg/kg dose of either DMPS or DMSA was injected (i.p.) 24 and 30 hr after treatment with HgCl2, the renal concentration and burden of inorganic mercury decreased markedly in both normal and NPX rats during the 24 hr after the first dose of the respective chelating agent was administered. Treatment with DMPS was more effective than treatment with DMSA in reducing the renal burden of mercury in both groups of rats. The fall in the renal concentration and burden of mercury in both normal and NPX rats was due primarily to a decrease in the content of mercury in the renal cortex and outer stripe of the outer medulla. However, the decrease in the concentration of inorganic mercury in the outer stripe was significantly greater in NPX rats than in normal rats. Both chelating agents caused urinary excretion of mercury to increase significantly in normal and NPX rats. In association with the increased renal release of mercury in NPX rats, the urinary excretion of mercury per gram of kidney was significantly greater in NPX rats than in normal rats. These data indicate that the renal handling of DMPS and DMSA may be altered significantly after a substantial reduction in renal mass. Findings from the present study also show that treatment with DMPS, but not with DMSA, causes the content of mercury in the liver and cellular fraction of blood to decrease in normal and NPX rats. These findings indicate that there are significant differences in the extrarenal handling of these two chelating agents. The findings in the present study suggest that DMPS and DMSA are very effective agents in reducing the renal (and whole body) burden of inorganic mercury in normal and NPX rats.
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Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D008099:Liver / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics; D008628:Mercury / Q000493:pharmacokinetics* / Q000652:urine; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D004113:Succimer / Q000494:pharmacology*; D013997:Time Factors; D014494:Unithiol / Q000494:pharmacology*
D014494:Unithiol; D008627:Mercuric Chloride; D004113:Succimer; D008628:Mercury