Oxygen radicals, inflammation, and arthritis: pathophysiological considerations and implications for treatment.
A vast amount of circumstantial evidence implicates oxygen-derived free radicals, especially superoxide and hydroxyl radical (and to lesser extent, hydrogen peroxide), as mediators of inflammation and/or tissue destruction in inflammatory and arthritic disorders. The substrates for radical generation, namely properly stimulated phagocytic cells, transition metal catalysts, and (to a limited extent) ischemia, are all amply present, although there is no particular rheumatic disease in which a consistent abnormality of radical generation has been identified. These radical species can clearly degrade hyaluronic acid, modify collagen and perhaps proteoglycan structure and/or synthesis, alter and interact with immunoglobulins, activate enzymes and inactivate their inhibitors, and possibly participate in chemotaxis. In most situations, however, there is ample scavenging ability to detoxify these radicals before they hit their target, and many rheumatic disease drugs can decrease their production and/or effects. Despite the apparent sufficiency of natural scavengers and the lack of direct evidence that oxygen radicals are pathogenetically important, substantial pharmaceutical effort is still being made to develop free radical scavengers as therapeutic agents. Although individual free radicals die out quickly, rheumatologic interest in them has been sustained for nearly two decades.
Greenwald
R A
RA
Division of Rheumatology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism* / Q000502:physiology; D013482:Superoxide Dismutase / Q000627:therapeutic use
D016166:Free Radical Scavengers; D005609:Free Radicals; D013482:Superoxide Dismutase; D010100:Oxygen