MOBILIZATION OF HEAVY-METALS BY NEWER, THERAPEUTICALLY USEFUL CHELATING-AGENTS
MOBILIZATION OF HEAVY-METALS BY NEWER, THERAPEUTICALLY USEFUL CHELATING-AGENTS
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DOI：
10.1016/0300-483x(95)02965-b
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发表时间：
1995-03-31
期刊：
影响因子：
4.5
通讯作者：
APOSHIAN, MM
中科院分区：
文献类型：
--
作者：
APOSHIAN, HV;MAIORINO, RM;APOSHIAN, MM
本文综述了四种最常用的治疗铅、汞、砷等重金属和类金属中毒的螯合剂的优缺点、代谢和特异性。其中，CaNa（2）EDTA和二巯基丙醇（英国抗路易氏剂，BAL）正变得过时，并且可以预期被内消旋-2，3-二巯基琥珀酸取代（DMSA，琥珀酰）用于治疗铅中毒和通过2，3-二巯基-1-丙磺酸的钠盐（DMPS，Dimaval（R））用于治疗铅、汞或砷中毒，Meso-2，3-DMSA和DMPS在人体内的生物转化不同。尿中排泄的DMSA中超过90%以混合二硫化物的形式存在，其中DMSA的每个硫原子与L-半胱氨酸分子形成二硫键。DMPS给药后，尿中发现DMPS的非环状和环状二硫化物，Dimaval汞激发试验作为汞暴露的诊断试验，特别是低水平汞中毒，具有很大的前景。与未挑战的尿汞排泄相比，Dimaval挑战后的尿汞可能是低水平汞中毒的更好生物标志物。
Four chelating agents that have been used most commonly for the treatment of humans intoxicated with lead, mercury, arsenic or other heavy metals and metalloids are reviewed as to their advantages, disadvantages, metabolism and specificity. Of these, CaNa(2)EDTA and dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval(R)) for treating lead, mercury or arsenic intoxication, Meso-2,3-DMSA and DMPS are biotransformed differently in humans. More than 90% of the DMSA excreted in the urine is found in the form of a mixed disulfide in which each of the sulfur atoms of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS administration, however, acyclic and cyclic disulfides of DMPS are found in the urine, The Dimaval-mercury challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after Dimaval challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion.