Role of iron and influence of antiinflammatory drugs on oxygen-derived free radical production and reactivity.
The production of a potent hydroxylating species, presumed to be hydroxyl radical, was studied using hydroxylation of salicylate as a detector system. Oxygen-derived free radicals (ODFR) were generated by (a) autoxidation of ferrous-EDTA chelates and (b) enzymatically (xanthine oxidase/hypoxanthine). Hydroxylation by these ODFR-generating systems was inhibited by superoxide dismutase, hydroxyl radical scavengers and singlet oxygen quenchers. Low concentrations (1 mM-10 mM) of penicillamine stimulated hydroxylation by the autoxidation system, although higher concentrations were inhibitory; all concentrations were inhibitory in the enzymatic system. The chelating agents, diethylenetriamine pentaacetic acid and bathophenanthroline sulphonate, were inhibitory in both systems, as were the long acting anti-rheumatic drugs, gold sodium thiomalate and chloroquine. The mechanisms of hydroxyl radical generation described may have relevance to the mechanisms of ODFR generation occurring in vivo at sites of inflammation.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006900:Hydroxylation; D007501:Iron / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen; D012459:Salicylates / Q000378:metabolism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D002614:Chelating Agents; D005609:Free Radicals; D012459:Salicylates; D006861:Hydrogen Peroxide; D007501:Iron; D010100:Oxygen