Kohen R, Chevion M
Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.
Free Radic Res Commun. 1985;1(2):79-88. doi: 10.3109/10715768509056540.
The involvement of transition metal ions in paraquat toxicity was studied in bacterial model system. We show that the addition of micromolar, or lower, concentrations of copper dramatically enhanced the rate of bacterial inactivation. In contrast, the addition of chelating agents totally eliminated the killing of E. coli. No inactivation was observed under anaerobic exposure to paraquat, both in the absence and presence of copper. However, in the presence of copper, the anaerobic addition of hydrogen peroxide resulted in complete restoration of inactivation as under aerobiosis. Paraquat either produces superoxide ions or directly reduces bound copper ions in a catalytic mode. The reduced cuprous complexes react with hydrogen peroxide to locally form hydroxyl radicals (OH.) which are probably responsible for the deleterious effects. This study indicates the involvement of a site-specific metal-mediated Haber-Weiss mechanism in paraquat toxicity. It is in agreement with earlier observations that copper unusually enhance biological damage induced by either superoxide or ascorbate.
在细菌模型系统中研究了过渡金属离子与百草枯毒性的关系。我们发现，添加微摩尔或更低浓度的铜会显著提高细菌失活速率。相反，添加螯合剂则完全消除了对大肠杆菌的杀伤作用。在有无铜存在的情况下，厌氧暴露于百草枯时均未观察到失活现象。然而，在有铜存在的情况下，厌氧添加过氧化氢会导致失活现象完全恢复，如同在需氧条件下一样。百草枯要么产生超氧离子，要么以催化方式直接还原结合的铜离子。还原后的亚铜络合物与过氧化氢反应，在局部形成羟基自由基（OH·），这可能是造成有害影响的原因。这项研究表明，一种位点特异性的金属介导的哈伯-维希机制参与了百草枯的毒性作用。这与早期的观察结果一致，即铜异常增强了由超氧或抗坏血酸诱导的生物损伤。
