Chevion M, Korbashi P, Katzhandler J, Saltman P
Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.
Adv Exp Med Biol. 1990;264:217-22. doi: 10.1007/978-1-4684-5730-8_35.
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 the E. coli model 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.
最近已证明铜和铁在多种自由基诱导的损伤（包括百草枯诱导的生物损伤）中起重要的介导作用。据推测，这些过渡金属会发生循环氧化还原反应，并作为反复产生羟基自由基的中心，而羟基自由基是最终的有害因子。此外，我们已提供证据表明，常用的试剂（螯合剂、化学清除剂和保护酶）能有效保护细胞免受百草枯毒性的影响。在本研究中，我们使用大肠杆菌模型来开发一种新的方法，以保护细胞免受百草枯诱导的金属介导的细胞损伤。该方法是给予过量的锌（比铜多50倍），这会抑制百草枯的毒性作用。Lineweaver-Burk分析表明这种抑制作用具有竞争模式。所提出的机制涉及将具有氧化还原活性的铜（或铁）从其结合位点置换出来，从而转移自由基反复产生的位点。因此，应考虑使用氧化还原惰性金属来干预百草枯毒性以及其他金属介导的自由基诱导的损伤过程，这些金属的配体化学性质与铁和铜高度相似，但自身毒性相对较低。
