Tasende M S, Gale G R, Smith A B, Jones M M, Singh P K
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina 29401.
Res Commun Chem Pathol Pharmacol. 1992 Jun;76(3):323-39.
Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and the unesterified 2,3-dimercaptosuccinic acid (DMSA) were evaluated for relative reactivities against metallothionein (MT)-bound cadmium (Cd) in vitro by elution of the reaction products through Sephadex G-75 gel. After 3 hr of incubation, Mi-ADMS removed about 70% of the Cd from Cd-MT, and a new peak emerged which corresponded to that obtained by elution of a 2:1 molar mixture of Mi-ADMS and Cd. Only about 15% of the Cd was removed from Cd-MT by DMSA. After 24 hr of incubation with Mi-ADMS, no evidence remained of the presence of Cd-MT; all of the Cd was recovered in a very high molecular weight fraction and in a fraction corresponding to Cd ion. In contrast, after 24 hr of incubation with DMSA, 25% of the Cd was still present as Cd-MT, while the remainder eluted in a fraction corresponding to a 2:1 molar complex of DMSA and Cd. When Mi-ADMS was administered to Cd-bearing mice which had received an inhibitor of organic anion transport, probenecid (PBC) or sulfinpyrazone (SPZ), prior to administration of the monoester, there was a marked attenuation of the Cd mobilizing actions of Mi-ADMS as reflected in whole body Cd levels. Analysis of organ Cd concentrations revealed that PBC blocked primarily the mobilization of renal Cd by Mi-ADMS, while the principal action of SPZ in antagonizing the action of Mi-ADMS was on hepatic Cd mobilization. It was concluded that Mi-ADMS has a higher affinity for Cd in Cd-MT than does DMSA, and that the access of Mi-ADMS to intracellular Cd is, at least in part, mediated by the organic anion transport system.
通过Sephadex G - 75凝胶洗脱反应产物，在体外评估单异戊酯中 - 2,3 - 二巯基琥珀酸（Mi - ADMS）和未酯化的2,3 - 二巯基琥珀酸（DMSA）与金属硫蛋白（MT）结合的镉（Cd）的相对反应活性。孵育3小时后，Mi - ADMS从Cd - MT中去除了约70%的Cd，出现了一个新峰，该峰与通过洗脱Mi - ADMS和Cd的2:1摩尔混合物获得的峰相对应。DMSA仅从Cd - MT中去除了约15%的Cd。与Mi - ADMS孵育24小时后，没有证据表明存在Cd - MT；所有的Cd都在非常高的分子量级分和与Cd离子对应的级分中回收。相比之下，与DMSA孵育24小时后，25%的Cd仍以Cd - MT的形式存在，其余部分在与DMSA和Cd的2:1摩尔复合物对应的级分中洗脱。当在给予单酯之前，将Mi - ADMS给予接受有机阴离子转运抑制剂丙磺舒（PBC）或磺吡酮（SPZ）的含镉小鼠时，如全身Cd水平所示，Mi - ADMS的Cd动员作用明显减弱。器官Cd浓度分析表明，PBC主要阻断了Mi - ADMS对肾脏Cd的动员，而SPZ拮抗Mi - ADMS作用的主要作用是对肝脏Cd的动员。得出的结论是，Mi - ADMS在Cd - MT中对Cd的亲和力高于DMSA，并且Mi - ADMS进入细胞内Cd至少部分是由有机阴离子转运系统介导的。
