THE EFFECT OF TRANILAST OF THE GENERATION OF REACTIVE OXYGEN SPECIES

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The relative in vitro antioxidant efficacy of tranilast, a new orally active antiallergic agent, was examined by studying its effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes and the cell-free, xanthine-xanthine oxidase system. The species investigated were superoxide radical anion (O_2-), hydrogen peroxide (H_2O_2) and hydroxyl radical (OH^*). At concentrations comparable to therapeutic blood levels, tranilast reduced both H_2O_2 and OH^* levels. The inhibitory effect of tranilast was dose-dependent and all ROS levels examined were significantly decreased at the concentration of 100 μg/ml. This antioxidant effect of tranilast appeared to stem from its capability to scavenge ROS because the suppression of ROS was observed in both ROS generation systems at higher concentrations, even though the possibility existed that tranilast directly inhibited nicotineamide adenine dinucleotide phosphate oxidase and/or xanthine oxidase activity. This unique anti-inflammatory pharmacological activity of tranilast suggests its potential clinical application for allergic diseases complicated with inflammation.
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