The expanding role of oxygen free radicals in clinical medicine.
In 1969 McCord and Fridovich discovered superoxide dismutase, which converts the oxygen free radical O(2) (-) to hydrogen peroxide H(2)O(2). In the presence of excess O(2) (-), H(2)O(2) may then undergo further reduction to the highly toxic hydroxyl radical, OH(*). Since the description of this enzymatic process, there has been explosive growth in related biochemical research, which has now percolated through to clinical investigation. The hypoxanthine-xanthine oxidase system originally used as a radical production model has a close counterpart in the ischemia-reperfusion phenomenon purported to cause diseases of heart, brain and gastrointestinal tract, and free radicals are now known to have a critical role in postphagocytic bacterial killing. Prototypic deficiency diseases such as chronic granulomatous disease are now recognized. Some evidence indicates that excess states such as perhaps Batten's disease also occur, and environmental influences such as selenium and vitamin E deficiency may augment free radical levels. Many disorders including microvasculopathies, noncardiogenic pulmonary edema, glomerulopathies and radiation damage may owe part of their proximate pathogenesis to free radicals. Control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases.
D000818:Animals; D003327:Coronary Disease / Q000209:etiology; D005609:Free Radicals; D005767:Gastrointestinal Diseases / Q000209:etiology; D005921:Glomerulonephritis / Q000209:etiology; D006105:Granulomatous Disease, Chronic / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000209:etiology; D010100:Oxygen / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology; D012643:Selenium / Q000172:deficiency; D013482:Superoxide Dismutase / Q000502:physiology*; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D012643:Selenium; D010100:Oxygen