Twarog T, Cherian M G
Toxicol Appl Pharmacol. 1984 Mar 15;72(3):550-6. doi: 10.1016/0041-008x(84)90132-7.
The mobilization of lead (Pb) from Pb-exposed rats was examined following administration of dimercaptopropane sulfonate (DMPS). A dose-response study showed that the highest dose of DMPS (200 mumol/kg, ip) removed Pb from kidneys, liver, and bone, while the lower doses (25 and 50 mumol/kg) chelated Pb only from the kidneys. In experiments where DMPS was repeatedly injected to Pb-exposed rats, the maximum urinary excretion of Pb was observed within 24 hr after the first injection, with little effect in subsequent injections. Discontinuation of DMPS after the first injection (at a dose of 50 mumol DMPS/kg) caused renal Pb levels to increase until further injection of DMPS, several days later, which again mobilized Pb only from the kidneys. A single oral administration of 150 mumol DMPS/kg (a dose adjusted for specific chelation from the kidney) to rats, previously exposed to different doses of Pb resulted in a significant decrease of renal Pb in groups injected with more than 0.5 mg Pb/kg. A linear relationship was observed between renal Pb burden and urinary Pb excretion following chelation (r = 0.94, p less than 0.01). Thus, the specific removal of Pb from the kidney by DMPS treatment suggests a potential use of DMPS, a relatively nontoxic drug, for the estimation of renal Pb burden and also for treatment of Pb poisoning. Unlike other chelating agents, DMPS can be administered orally.
在给予二巯基丙磺酸钠(DMPS)后,对铅暴露大鼠体内铅(Pb)的动员情况进行了研究。剂量反应研究表明,DMPS的最高剂量(200 μmol/kg,腹腔注射)可使肾脏、肝脏和骨骼中的铅排出,而较低剂量(25和50 μmol/kg)仅能螯合肾脏中的铅。在对铅暴露大鼠反复注射DMPS的实验中,首次注射后24小时内观察到铅的最大尿排泄量,后续注射影响较小。首次注射(剂量为50 μmol DMPS/kg)后停止使用DMPS会导致肾脏铅水平升高,直到数天后再次注射DMPS,此时铅又仅从肾脏中被动员出来。对先前暴露于不同剂量铅的大鼠单次口服150 μmol DMPS/kg(根据从肾脏中特异性螯合调整的剂量),在注射超过0.5 mg Pb/kg的组中,肾脏铅含量显著降低。螯合后观察到肾脏铅负荷与尿铅排泄之间呈线性关系(r = 0.94,p < 0.01)。因此,DMPS治疗可特异性地从肾脏中去除铅,这表明相对无毒的药物DMPS在评估肾脏铅负荷以及治疗铅中毒方面具有潜在用途。与其他螯合剂不同,DMPS可以口服给药。