Inhibition of peroxidase activity by some non-steroidal anti-inflammatory drugs

Abstract

The non-steroidal anti-inflammatory drugs, indomethacin, flufenamic acid and naproxen inhibited thyroid peroxidase-catalyzed iodination of BSA in vitro. Inhibition by all three drugs was affected more effectively in a hydrogen peroxide generating system than in an incubation system in which hydrogen peroxide was added. Naproxen differed from the other two drugs in so far as it inhibited mainly hydrogen peroxide generation while its comparatively low inhibitory influence (>20%) on TPO was not dose-dependent. The inhibitory influence of these anti-inflammatory drugs was also observed when other peroxidases, such as lactoperoxidase, chloroperoxidase and horseradish peroxidase were used for catalyzing BSA iodination in a hydrogen peroxide generating system. No iodination of BSA was obtained with horseradish peroxidase when hydrogen peroxide was added instead of generated so that the inhibitory nature of these drugs could not distinguish between their direct effect on horseradish peroxidase or on hydrogen peroxide generation. However, in lactoperoxidase and chloroperoxidase-catalyzed BSA iodinations in non-H 2O 2-generating systems naproxen had no appreciable inhibitory influence below a 1 millimolar concentration. On another thyroid peroxidase activity, namely its catalyzing influence on the exchange reaction between inorganic iodide and organic iodine in diiodotyrosine, indomethacin and naproxen showed unappreciable effects lower than 1 mM concentrations. Similarly, on thyroid peroxidase and lactoperoxidasecatalyzed deiodination of thyroxine they were ineffective inhibitors. The data suggest that these antiinflammatory drugs are effective inhibitors of iodination reactions but ineffective inhibitors of deiodination reactions.