Kappus H
Arch Toxicol. 1987;60(1-3):144-9. doi: 10.1007/BF00296968.
The toxic effects of compounds which undergo redox cycling via enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.
本文综述了通过酶促单电子还原进行氧化还原循环的化合物的毒性作用。首先，这些化合物的酶促还原会产生反应性中间体，主要是与氧反应的自由基，从而形成超氧阴离子自由基。进一步的氧代谢产物是过氧化氢、单线态氧和羟基自由基。讨论了这些氧代谢产物在毒性中的作用。对醌类化合物（如阿霉素）氧化还原循环过程中脂质过氧化的发生及其与毒性的可能关系进行了批判性评估。结果表明，铁离子在氧化还原循环化合物诱导的脂质过氧化中起关键作用。基于观察到博来霉素 - 铁复合物的酶促氧化还原循环这一发现，讨论了金属螯合物（如博来霉素）对DNA的损伤。有人声称羟基自由基参与了细胞核氧化还原循环过程中博来霉素诱导的DNA损伤。还讨论了其他物质（如芳香胺）的氧化还原循环与致癌作用的关系。其他化学基团，如硝基芳香化合物、羟胺和偶氮化合物也包括在内。还涉及了氧自由基攻击的其他靶点，如蛋白质。结论是，如果细胞的保护机制不堪重负，氧化还原循环产生的氧自由基可能是几种化合物毒性作用中的关键事件。
