Kostyniak P J
J Toxicol Environ Health. 1983 Apr-Jun;11(4-6):947-57. doi: 10.1080/15287398309530397.
2,3-Dimercaptosuccinic acid (DMSA) has been utilized in chelation therapy and in extracorporal complexing hemodialysis therapy for experimental methylmercury intoxication. In the latter application, substantial excretion of methylmercury occurred by the urinary route. This prompted the current study of the effects of continuous intravenous DMSA infusion therapy on methylmercury kinetics in the dog. Animals previously dosed with 203Hg-labeled methylmercury at 2.5 mg Hg/kg received a priming dose of DMSA, followed by a continuous iv infusion at dose rates that resulted in DMSA concentrations in plasma similar to those observed during DMSA complexing hemodialysis therapy. The kinetics of 203Hg removal in DMSA-infused dogs was compared with both saline-infused controls and DMSA complexing hemodialysis treated dogs. DMSA infusion therapy resulted in a shift in 203Hg binding within systemic blood from the red-cell fraction into plasma. This was consistent with an observed association of DMSA with the plasma fraction. The shift in 203Hg from red cells into plasma was paralleled by an increase in urinary clearance of 203Hg during the DMSA infusion period. In four dogs treated in this fashion, an average of 6.5 micrograms of mercury was removed by the urinary route over the 5-h treatment period, compared to 0.007 micrograms in the saline-infused dogs. Although a similar magnitude of mercury output into urine was observed during DMSA complexing hemodialysis, an additional 5 micrograms was removed by the dialyzer, making that technique 1.5 times as effective as infusion therapy. Comparing 203Hg tissue concentration after DMSA infusion therapy with the saline-treated controls revealed a 6.5-fold decrease in liver, a 3-fold reduction in kidney, and a 27% reduction in cerebrum. No significant differences were observed in medulla or cerebellum. Histopathology revealed no consistent differences between DMSA-treated and saline-treated animals. The DMSA infusion therapy was effective in causing a rapid removal of 203Hg from animals previously dosed with 203Hg-labeled methylmercury. DMSA infusion therapy may provide a useful therapeutic alternative for methylmercury poisoning when rapid removal of the intoxicant is desired and hemodialysis equipment and expertise are not readily available.
2,3-二巯基丁二酸（DMSA）已被用于螯合疗法以及用于实验性甲基汞中毒的体外络合血液透析疗法。在后一种应用中，甲基汞通过尿液途径大量排泄。这促使了当前对连续静脉输注DMSA疗法对犬体内甲基汞动力学影响的研究。之前以2.5毫克汞/千克的剂量给予203Hg标记甲基汞的动物接受了一次DMSA的起始剂量，随后以能使血浆中DMSA浓度与DMSA络合血液透析疗法中观察到的浓度相似的剂量率进行连续静脉输注。将输注DMSA的犬体内203Hg清除的动力学与输注生理盐水的对照犬以及接受DMSA络合血液透析治疗的犬进行了比较。DMSA输注疗法导致全身血液中203Hg的结合从红细胞部分转移到血浆中。这与观察到的DMSA与血浆部分的结合情况一致。在DMSA输注期间，203Hg从红细胞向血浆的转移与203Hg尿清除率的增加同时出现。以这种方式治疗的4只犬在5小时的治疗期间平均通过尿液途径排出了6.5微克汞，而输注生理盐水的犬排出了0.007微克。尽管在DMSA络合血液透析期间观察到进入尿液的汞量相似，但透析器额外清除了5微克，这使得该技术的效果是输注疗法的1.5倍。将DMSA输注疗法后203Hg的组织浓度与生理盐水处理的对照进行比较，发现肝脏中降低了6.5倍，肾脏中降低了3倍，大脑中降低了27%。在髓质或小脑中未观察到显著差异。组织病理学显示DMSA处理的动物和生理盐水处理的动物之间没有一致的差异。DMSA输注疗法有效地使之前给予203Hg标记甲基汞的动物体内的203Hg快速清除。当需要快速清除中毒物质且血液透析设备和专业技术不易获得时，DMSA输注疗法可能为甲基汞中毒提供一种有用的治疗选择。
