Effect of metal chelators and antiinflammatory drugs on the degradation of hyaluronic acid.
Degradation of hyaluronic acid (measured viscometrically) by oxygen-derived free radicals (ODFR) generated 1) by autoxidation of ferrous EDTA chelates and 2) enzymatically by xanthine oxidase and hypoxanthine (XO/HX) was studied. Degradation of hyaluronic acid by XO/HX was strongly inhibited by superoxide dismutase and catalase, whereas degradation of hyaluronic acid by autoxidation of ferrous ions was weakly inhibited by catalase and unaffected by superoxide dismutase. Both ODFR-producing systems were inhibited by hydroxyl radical scavengers, suggesting that hydroxyl radical was the proximate damaging species in both systems. Penicillamine at concentrations of 1-5 mM stimulated hyaluronic acid degradation by ferrous EDTA chelates but inhibited degradation by the XO/HX system. Higher concentrations of penicillamine and all concentrations studied (1-100 mM) of other antiinflammatory drugs (chloroquine, gold sodium thiomalate, and salicylate) inhibited hyaluronic acid degradation by both the autoxidation and enzymatic ODFR-producing systems, with inhibitory potency similar to that seen with known hydroxyl radical scavengers. Both systems serve as in vitro models of ODFR-mediated tissue damage which may occur in vivo at sites of inflammation.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D007042:Hypoxanthines / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014783:Viscosity; D014969:Xanthine Oxidase / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007042:Hypoxanthines; D007502:Iron Chelating Agents; D006820:Hyaluronic Acid; D004492:Edetic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase