© 1983 Oxford University Press
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Fuatile Redox Cycling: Implications for Oxygen Radical Toxicity
Institute for Toxicology and Department of Biochemistry, University of Southern California Los Angeles, CA 90033
Futile Redox Cycling: Implications for Oxygen Radical Toxicity. Hochstein, P. (1983). Fundam. Appl. Toxicol. 3:215-217. The reduction and the potential autoxidation of quinoid compounds may be viewed as taking place in three cell compartments. In microsomal fractions (endoplasmic reticulum) one-electron reduction by NADPH-cytochrome P450 reductase leads to the formation of semiquinones which rapidly react with oxygen to form the parent quinone and superoxide anions. The formation of superoxide through this futile cycle leads ultimately to other damaging species (H2O2 and OH). A similar futile cycle in mitochondria involves NADH dehydrogenase. In this instance, mitochon-drial initiation of such a cycle with quinones results not only in the formation of toxic radical species but also in the diversion of electrons from phosphory lating pathways. The consequent diminution of cellular ATP may have as important a consequence with respect to the toxicity of quinones as the generation of radicals. Finally, cytosolic DT diaphorase, which carries out a two-electron reduction of quinones to more stable hydroquinones, may compete with the one-electron systems and participate in the detoxification of quinones by supplying hydroquinones for conjugation reactions. The extent of quinone-induced damage may thus vary from cell to cell depending on the integration of these pathways.