Determination and metabolism of dithiol chelating agents. VII. Biliary excretion of dithiols and their interactions with cadmium and metallothionein.
Determination and metabolism of dithiol chelating agents. VII. Biliary excretion of dithiols and their interactions with cadmium and metallothionein.
复制标题
二硫醇螯合剂的测定和代谢。
DOI：
10.1016/0272-0590(90)90264-k
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Aposhian,HV
中科院分区：
文献类型：
--
作者：
Zheng,W;Maiorino,RM;Brendel,K;Aposhian,HV
二硫醇螯合剂的测定和代谢。七.二硫醇的胆汁排泄及其与镉和金属硫蛋白的相互作用。郑伟，马约里诺河M.，布伦德尔，K.，和Aposhian，H。V.（1990）. Fundament. N-（2，3-二巯基丙基）邻苯二甲酸（DMPA）、内消旋-二巯基琥珀酸（DMSA）和2，3-二巯基-1-丙磺酸（DMPS）是对铅、汞、砷和其它重金属具有解毒活性的二硫醇螯合剂。在雄性Sprague-Dawley大鼠中研究了这些化合物的胆汁排泄。DM PA静脉给药后，胆汁中回收了注射剂量的72%。回收的DMPA的一半为未改变的形式（母体化合物），另一半为改变的形式（DTT化学还原后回收的母体化合物）。在胆汁中发现了DMPS的一种改变形式（可能是二硫化物）。胆汁中未检测到未改变或改变的DMSA。DMPA（0.10 mmol/kg），给予大鼠暴露于镉3天后，在30分钟内引起胆汁镉排泄量增加20倍。DMPA引起的胆汁Cd的增加与剂量有关，而不是由于胆汁流速的增加。DMSA和DMPS对镉的胆汁排泄无显著影响。DMPA或DMSA与镉饱和的金属硫蛋白（MT）孵育，导致从MT中去除镉。DMPA在这方面比DMSA更积极。这一证据有力地支持了DMPA给药后胆汁中镉含量增加的机制，即DMPA进入细胞并动员和清除MT中的镉。二巯基螯合剂从金属硫蛋白中去除镉为其作用机制提供了另一个维度，并可能为镉和金属硫蛋白的研究提供重要的新工具。
Determination and Metabolism of Dithiol Chelating Agents. VII. Biliary Excretion of Dithiols and Their Interactions with Cadmium and Metallothionein. ZHENG, W., MAIORINO, R. M., BRENDEL, K., AND APOSHIAN, H. V. (1990).Fundam. Appl. Toxicol.14, 598–607.N-(2,3-Di-mercaptopropyl) phthalamidic acid (DMPA),meso-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propanesulfonic acid (DMPS) are dithiol chelating agents with antidotal activity for lead, mercury, arsenic, and other heavy metals. The biliary excretion of these compounds was studied in male Sprague-Dawley rats. After iv administration of DM PA, 72% of the injected dose was recovered in the bile. Half of the recovered DMPA was in the unaltered form (parent compound) and the other half was in the altered form (parent compound recovered after chemical reduction by DTT). An altered, presumably disulfide, form of DMPS was found in the bile. Neither unaltered nor altered DMSA was detected in the bile. DMPA (0.10 mmol/kg), given to rats 3 days after exposure to Cd, elicited within 30 min a 20-fold increase in biliary Cd excretion. The increase of biliary Cd by DMPA was dose-related and not due to an increase of bile flow rate. DMSA and DMPS did not significantly affect the biliary excretion of Cd. Incubation of DMPA or DMSA with Cd-saturated metallothionein (MT) resulted in the removal of Cd from MT. DMPA was more active than DMSA in this respect. The evidence strongly supports the mechanism that the increase of biliary cadmium following DMPA administration is the result of DMPA entering cells and mobilizing and removing the cadmium from MT. The removal of cadmium from metallothionein by dithiol chelating agents provides another dimension to their mechanisms of action and may provide an important new tool for the study of cadmium as well as metallothionein.