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.