In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine
In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine
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DOI：
10.1016/0891-5849(96)00020-2
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发表时间：
1996-01-01
影响因子：
7.4
通讯作者：
Spitz, DR
中科院分区：
文献类型：
--
作者：
Ercal, N;Treeratphan, P;Spitz, DR
铅的能力破坏哺乳动物组织内的促氧化剂/抗氧化剂的平衡的知识表明，慢性铅中毒的决定性治疗应包括螯合和抗氧化作用。二硫醇内消旋-2，3-二巯基琥珀酸（DMSA）是第一种获得美国食品和药物管理局（FDA）批准用于治疗儿童铅中毒的口服金属螯合剂，具有通过去除铅而发挥抗氧化剂作用的潜力。有害氧化反应部位。五个星期的铅暴露被发现消耗谷胱甘肽（GSH）水平，增加氧化型谷胱甘肽（GSSG），并促进丙二醛（MDA）的生产在肝脏和大脑样本取自C57 BL/6小鼠。铅暴露小鼠在处死前给予1 mmol/kg DMSA或5.5 mmol/kg N-乙酰半胱氨酸（NAG）7 d，GSH水平升高，GSSG和MDA水平降低。用DMSA治疗引起血液、肝脏和大脑铅水平的降低，这与其作为螯合剂的功能一致，而用NAC治疗并没有降低这些铅水平。然而，NAC确实导致脑和肝脏样品中氧化应激指数的降低，这意味着这种合成的含巯基抗氧化剂能够消除体内铅诱导的氧化应激。总体而言，这些结果表明，铅诱导的氧化应激在体内可以减轻药物干预，其中包括螯合以及硫醇介导的抗氧化功能。
Knowledge of lead's capacity to disrupt the prooxidant/antioxidant balance within mammalian tissues suggests that definitive therapy for chronic lead poisoning should encompass both chelating and antioxidant actions. The dithiol meso-2,3-Dimercaptosuccinic Acid (DMSA) is the first orally administered metal chelating agent to receive U.S. Food and Drug Administration (FDA) approval for the treatment of childhood plumbism and possesses the potential to function as an antioxidant by removing lead from the site of deleterious oxidation reactions. Five weeks of lead exposure was found to deplete glutathione (GSH) levels, increase oxidized glutathione (GSSG), and promote malondialdehyde (MDA) production in both liver and brain samples taken from C57BL/6 mice. GSH levels increased and GSSG and MDA levels decreased in groups of lead-exposed mice that received 1 mmol/kg DMSA or 5.5 mmol/kg N-acetylcysteine (NAG) for 7 d prior to sacrifice. Treatment with DMSA caused a reduction in blood, liver, and brain lead levels consistent with its function as a chelating agent, while treatment with NAC did not reduce these lead levels. However, NAC did cause a reduction in indices of oxidative stress in both brain and Liver samples, which implies that this synthetic thiol-containing antioxidant is capable of abrogating lead-induced oxidative stress in vivo. Overall, these results suggest that lead-induced oxidative stress in vivo can be mitigated by pharmacologic interventions, which encompass both chelating as well as thiol-mediated antioxidant functions.