Zalups R K, Gelein R M, Cernichiari E
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
J Pharmacol Exp Ther. 1991 Jan;256(1):1-10.
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.
在单侧肾切除(NPX)和假手术(SO)大鼠中研究了2,3-二巯基丙烷-1-磺酸盐(DMPS)作为氯化汞诱导的急性肾病抢救剂的有效性。给予2.5 μmol/kg毒性剂量氯化汞的NPX和SO大鼠在给予氯化汞后24小时内出现严重肾损伤。通过测量血浆肌酐、肌酐清除率、几种生物标志物的分数排泄、细胞酶和血浆溶质的排泄率以及近端小管直部形态学可证实的坏死严重程度来评估肾损伤。在用2.5 μmol/kg剂量的氯化汞处理1小时后,给NPX和SO大鼠给予10 mg/kg剂量的DMPS,该剂量的氯化汞诱导的肾病不太严重。此外,NPX大鼠的肾损伤明显比SO大鼠轻。在用2.5 μmol/kg剂量的氯化汞处理1小时后,给NPX和SO大鼠给予100 mg/kg剂量的DMPS,这两组大鼠均完全没有肾损伤。这些数据表明,在10 mg/kg剂量的DMPS下,NPX大鼠比SO大鼠在更大程度上受到保护,免受2.5 μmol/kg剂量氯化汞的肾毒性作用。此外,数据表明,在用氯化汞处理后1小时内给予100 mg/kg DMPS的NPX和SO大鼠,可从2.5 μmol/kg剂量的氯化汞诱导的损伤中完全恢复。这种完全恢复至少可持续24小时。基于目前的研究结果,DMPS可能被证明是一种有效的抢救剂,可对抗氯化汞诱导的急性肾病。