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RK Zalups, RM Gelein and E Cernichiari
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
The effectiveness of 2,3-dimercaptopropane-1-sulfonate (DMPS) as a rescue agent for the acute nephropathy induced by HgCl2 was studied in uninephrectomized (NPX) and sham-operated (SO) rats. NPX and SO rats that were given a toxic 2.5-mumol/kg dose of HgCl2 developed severe renal damage within 24 hr after the HgCl2 was administered. Renal injury was assessed by measuring plasma creatinine, creatinine clearance, fractional excretion of several biological markers, the rate of excretion of cellular enzymes and plasma solutes and severity of morphologically demonstrable necrosis in the pars recta of proximal tubules. When a 10-mg/kg dose of DMPS was given to the NPX and SO rats 1 hr after treatment with the 2.5-mumol/kg dose of HgCl2, the nephropathy induced by the dose of HgCl2 was less severe. Moreover, the NPX rats had significantly less severe renal damage than did the SO rats. Renal damage was completely absent from both NPX and SO rats that were given a 100-mg/kg dose of DMPS 1 hr after treatment with the 2.5- mumol/kg dose of HgCl2. These data indicate that at the 10-mg/kg dose of DMPS, NPX rats are protected against the nephrotoxic effects of a 2.5-mumol/kg dose of HgCl2 to a greater extent than are SO rats. Moreover, the data show that complete rescue from the 2.5-mumol/kg dose of HgCl2 is afforded to NPX and SO rats given 100 mg/kg of DMPS within 1 hr after treatment with HgCl2. This complete rescue is afforded for at least 24 hr. Based on the present findings DMPS may prove to be a useful rescue agent against the acute nephropathy induced by HgCl2.
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  R. K. Zalups Molecular Interactions with Mercury in the Kidney Pharmacol. Rev., March 1, 2000; 52(1): 113 - 144. [Abstract] [Full Text] [PDF]
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 R. K. Zalups, L. D. Parks, V. T. Cannon, and D. W. Barfuss Mechanisms of Action of 2,3-Dimercaptopropane-1-sulfonate and the Transport, Disposition, and Toxicity of Inorganic Mercury in Isolated Perfused Segments of Rabbit Proximal Tubules Mol. Pharmacol., August 1, 1998; 54(2): 353 - 363. [Abstract] [Full Text]
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L. H. Lash, D. A. Putt, and R. K. Zalups Role of Extracellular Thiols in Accumulation and Distribution of Inorganic Mercury in Rat Renal Proximal and Distal Tubular Cells J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1039 - 1050. [Abstract] [Full Text]
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