Abstract

Tungsten (W) and its compounds have emerged as a relatively new area of environmental health concern in the last decade. Tungsten is environmentally benign due to its increasing use in armour-piercing munitions and as a replacement for lead in other ammunition. It has also been identified in various hazardous waste sites and therefore been proposed for inclusion in the Environmental Protection Agency National Priorities List. The major objective of this study was to evaluate the therapeutic efficacy of orally administered monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) against tungstate induced oxidative injury in blood, liver and kidneys of male Wistar rats. MiADMSA, a thiol chelator has gained wide recognition recently as a future chelating drug of choice specifically for arsenic and was chosen for this study as tungstate ions too have an affinity toward the –SH group thus, being less bioavailable in the body. We determined the effects of MiADMSA (50 mg/kg, p.o.) against sodium tungstate (500 ppm in drinking water, daily for 28 days) induced biochemical changes indicative of oxidative stress in blood, and other soft tissues of of male Wistar rats. Tungsten exposure led to an increased levels of Reactive Oxygen Species (ROS) in liver, kidney, spleen and blood accompanied also by an increase in TBARS levels. The GSH: GSSG ratio also showed a decrease on sodium tungstate intoxication. Treatment with MiADMSA restored most of the sodium tungstate-induced alterations in the biomarkers suggestive of oxidative stress. These preliminary results led us to conclude that sub-acute exposure to tungstate-induced oxidative stress could be effectively reduced by the administration of MiADMSA and thus might be a promising antidote for studying in detail its efficacy in reducing body tungstate burden and its excretion post tungstate exposure.

摘要

在过去十年中，钨 (W) 及其化合物已成为环境健康关注的一个相对较新的领域。钨对环境无害，因为它越来越多地用于穿甲弹药并替代其他弹药中的铅。它也已在各种危险废物场所中被发现，因此被提议列入环境保护署国家优先事项清单。本研究的主要目的是评估口服单异戊基 2, 3-二巯基丁二酸 (MiADMSA) 对钨酸盐诱导的雄性 Wistar 大鼠血液、肝脏和肾脏氧化损伤的治疗效果。米阿德姆萨，硫醇螯合剂最近作为一种专门针对砷的未来螯合药物获得了广泛认可，并被选择用于本研究，因为钨酸盐离子也对 -SH 基团具有亲和力，因此在体内的生物利用度较低。我们确定了 MiADMSA（50 mg/kg，口服）对钨酸钠（饮用水中 500 ppm，每天 28 天）诱导的生化变化的影响，这些变化表明雄性 Wistar 大鼠血液和其他软组织中的氧化应激。钨暴露导致肝脏、肾脏、脾脏和血液中活性氧 (ROS) 水平升高，同时 TBARS 水平也升高。GSH：GSSG 比率也显示出钨酸钠中毒的降低。用 MiADMSA 治疗恢复了大部分钨酸钠诱导的提示氧化应激的生物标志物的变化。这些初步结果使我们得出结论，通过给予 MiADMSA 可以有效减少亚急性暴露于钨酸盐诱导的氧化应激，因此可能是详细研究其在减少体内钨酸盐负荷及其钨酸盐后排泄方面的功效的有希望的解毒剂暴露。