Zalups R K
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
J Pharmacol Exp Ther. 1993 Nov;267(2):791-800.
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.
在正常大鼠和单侧肾切除（NPX）大鼠中，静脉注射无毒剂量0.5 μmol/kg的氯化汞（HgCl₂）后，研究了水溶性螯合剂2,3-二巯基-1-丙烷磺酸盐（DMPS）和内消旋-2,3-二巯基琥珀酸（DMSA）对无机汞肾脏处置的影响。在用HgCl₂处理24和30小时后，腹腔注射100 mg/kg剂量的DMPS或DMSA，在给予各自螯合剂首剂后的24小时内，正常大鼠和NPX大鼠肾脏中无机汞的浓度和负荷均显著降低。在两组大鼠中，DMPS治疗在降低汞的肾脏负荷方面比DMSA治疗更有效。正常大鼠和NPX大鼠肾脏中汞浓度和负荷的下降主要是由于肾皮质和外髓质外层汞含量的减少。然而，NPX大鼠外髓质外层无机汞浓度的下降明显大于正常大鼠。两种螯合剂均使正常大鼠和NPX大鼠的尿汞排泄显著增加。与NPX大鼠肾脏汞释放增加相关，NPX大鼠每克肾脏的尿汞排泄量显著高于正常大鼠。这些数据表明，肾脏质量大幅减少后，DMPS和DMSA的肾脏处理可能会发生显著改变。本研究结果还表明，DMPS治疗而非DMSA治疗可使正常大鼠和NPX大鼠肝脏和血液细胞部分的汞含量降低。这些发现表明，这两种螯合剂在肾外处理方面存在显著差异。本研究结果表明，DMPS和DMSA是降低正常大鼠和NPX大鼠肾脏（及全身）无机汞负荷非常有效的药物。
