Antioxidant role of α-lipoic acid in lead toxicity
Antioxidant role of α-lipoic acid in lead toxicity
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DOI：
10.1016/s0891-5849(99)00036-2
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发表时间：
1999-07-01
影响因子：
7.4
通讯作者：
Ercal, N
中科院分区：
文献类型：
--
作者：
Gurer, H;Ozgunes, H;Ercal, N
氧化应激作为铅中毒机制的假设表明，抗氧化剂可能在铅中毒的治疗中发挥作用。本研究旨在探讨在铅暴露的中国仓鼠卵巢（CHO）细胞和Fischer 344大鼠中，硫辛酸（LA）在重新平衡增加的促氧化剂/抗氧化剂比例方面的功效。此外，LA的能力，以降低铅治疗大鼠的血液和组织中的铅水平进行了检查。LA管理导致在一个显着的改善，通过增加谷胱甘肽水平和降低丙二醛水平的铅暴露的细胞和动物的细胞的巯基容量，表明一个强大的抗氧化剂转移铅诱导的氧化应激。此外，铅治疗后给予LA显着降低过氧化氢酶和红细胞葡萄糖-6-磷酸脱氢酶活性。在体外给药的LA CHO细胞培养物显着增加细胞的存活率，这是抑制铅治疗的浓度依赖性的方式。与能够将其降低至对照水平的众所周知的螯合剂琥珀酰亚胺相比，LA的施用在降低血液或组织铅水平方面无效。因此，LA似乎是一个很好的候选人的治疗干预铅中毒，结合螯合剂，而不是作为一个单一的代理。(C)1999 Elsevier Science Inc.
The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentration-dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent. (C) 1999 Elsevier Science Inc.