Blanusa M, Kostial K, Piasek M, Jones M M, Singh P K
Department of the Physiology of Mineral Metabolism, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Analyst. 1995 Mar;120(3):951-3. doi: 10.1039/an9952000951.
The mono-3-methylbutan-1-yl (monoisoamyl) ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) was previously found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in mobilizing cadmium and mercury deposits in young and adult mice and rats. It was also tested to mobilize lead in and adult mice. It was also tested to mobilized lead in adult mice. The purpose of this study was to evaluate the ability of Mi-ADMS to chelate lead at a very young age, in sucking rats. Lead was applied intraperitoneally at the dose of 5 mg kg-1 in the form of lead acetate to six-day-old rats. Treatment with DMSA and Mi-ADMS was administered orally at the dose of 0.25 mmol kg-1, either as early (0.5 and 24 h) or a delayed (4th and 5th day after lead application) therapy. At the end of the experiment (6th day) lead was determined by atomic absorption spectrometry in the skeleton, liver, kidney and brain of the animals. Results showed that Mi-ADMS was more efficient than DMSA after early application in reducing the skeletal, kidney and brain content of lead. After delayed application it was either (skeleton and kidneys) or better (brain) than DMSA. There was no statistically significant influence of either chelator on liver lead content. The major finding is that Mi-ADMS at low doses causes a much higher reduction in brain retention of lead in sucklings than DMSA. This is important because the brain is considered to be the target organ of lead toxicity in the youngest age group.
先前发现内消旋-2,3-二巯基琥珀酸的单-3-甲基丁-1-基（单异戊基）酯（Mi-ADMS）在动员幼年和成年小鼠及大鼠体内的镉和汞沉积物方面优于内消旋-2,3-二巯基琥珀酸（DMSA）。还对其在成年小鼠体内动员铅的能力进行了测试。本研究的目的是评估Mi-ADMS在极幼年的乳鼠体内螯合铅的能力。以醋酸铅的形式给6日龄大鼠腹腔注射5 mg kg-1剂量的铅。以0.25 mmol kg-1的剂量口服给予DMSA和Mi-ADMS进行治疗，治疗时间可早（铅注射后0.5和24小时）或延迟（铅注射后第4天和第5天）。在实验结束时（第6天），通过原子吸收光谱法测定动物骨骼、肝脏、肾脏和大脑中的铅含量。结果表明，早期应用后，Mi-ADMS在降低骨骼、肾脏和大脑中的铅含量方面比DMSA更有效。延迟应用后，其在骨骼和肾脏方面与DMSA相当，在大脑方面优于DMSA。两种螯合剂对肝脏铅含量均无统计学上的显著影响。主要发现是，低剂量的Mi-ADMS比DMSA能使乳鼠大脑中铅的潴留量降低得多。这一点很重要，因为大脑被认为是最年幼年龄组中铅毒性的靶器官。
