Free radicals in toxicology: redox cycling and NAD(P)H:quinone oxidoreductase.

Abstract

Redox cycling compounds are among the multiple sources of free radicals generated in situations of toxicological interest. These compounds can undergo one-electron reduction to autoxidizable radical intermediates. The radicals react with oxygen to form the superoxide anion radical which can disproportionate to hydrogen peroxide and give rise to further oxidants. The other product of the autoxidation reaction is the parent compound, ready to go through further reaction cycles. One-electron reductions are frequently catalyzed by the electron-transfer chain of the endoplasmatic reticulum, the electron being supplied by NADPH. Detoxication of hydrogen peroxide utilizes NADPH as well in the GSSG reductase reaction. In this fashion, the cellular pool of NADPH may become severely depleted during redox cycling, enhancing toxicity. Toxic drugs of this type include quinones and nitroaromatics (for a review, see Kappus and Sies, 1981).KeywordsRenal Cell CarcinomaRedox CyclingCytostatic DrugQuinone OxidoreductaseNitroaromatic CompoundThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.