Zinc--a redox-inactive metal provides a novel approach for protection against metal-mediated free radical induced injury: study of paraquat toxicity in E. coli.
Zinc--a redox-inactive metal provides a novel approach for protection against metal-mediated free radical induced injury: study of paraquat toxicity in E. coli.
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锌——一种氧化还原惰性金属，提供了一种防止金属介导的自由基诱导损伤的新方法：百草枯对大肠杆菌的毒性研究。
DOI：
10.1007/978-1-4684-5730-8_35
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发表时间：
1990
影响因子：
--
通讯作者：
Saltman,P
中科院分区：
文献类型：
--
作者：
Chevion,M;Korbashi,P;Katzhandler,J;Saltman,P
铜和铁在各种自由基诱导的损伤，包括百草枯诱导的生物损伤中的重要介导作用最近已被证明。据推测，这些过渡金属进行循环氧化还原反应，并作为中心的羟基自由基的重复生产，这是最终的有害试剂。此外，我们提出的证据表明，有效的保护对百草枯毒性的常用代理（螯合剂，化学清除剂和保护酶）。在这项研究中，我们使用的E. Coil模型，以发展一种新的方法，对百草枯诱导的金属介导的细胞损伤的保护。它需要施用过量的锌（高达铜的50倍），从而抑制百草枯的毒性作用。Lineweaver-Burk分析证明了这种抑制作用的竞争模式.建议的机制涉及的氧化还原活性铜（或铁）从其结合位点的位移，并通过这种转移的网站重复生产的自由基。因此，应考虑使用与铁和铜的配体化学性质高度相似、但本身毒性相对较低的氧化还原惰性金属来干预百草枯毒性和其他金属介导的自由基诱导的有害过程。
The essential mediatory role of copper and iron in a variety of free radical-induced injuries, including paraquat-induced biological damage has been recently demonstrated. It was postulated that these transition metals undergo cyclic redox reactions, and serve as centers for repeated production of hydroxyl radical, which are the ultimate deleterious agents. Additionally, we had presented evidence indicating efficient protection against paraquat toxicity by agents commonly employed (chelators, chemical scavengers and protecting enzymes).In this study we have used theE.Coilmodel in order to develop a new approach for protection against paraquat-induced metal-mediated cellular injury. It entails the administration of excess zinc (up to 50 fold over copper), which results in an inhibition of the toxic effect of paraquat. Lineweaver- Burk analysis demonstrates the competitive mode of this inhibition. The suggested mechanism involves the displacement of the redox-active copper (or iron) from its binding site and by this diverting the site of repeated production of free radicals. Thus, use of redox-inactive metals, which possess high similarity of their ligand chemistry, to that of iron and copper but are of relative low toxicity by themselves, should be considered for intervention in paraquat toxicity and in other metal-mediated free radical-induced injurious processes.