Mechanisms of active oxygen species reduction by non-steroidal anti-inflammatory drugs

Many forms of active oxygen have been suggested to participate in the course of inflammation. Anti-inflammatory drugs have been considered to function as active oxygen inhibitors. However, detailed mechanisms for such inhibitory activity remain unclear because of little well established methods to study inhibitory effect of anti-inflammatory drugs on active oxygen species. In this report, the author investigated four non-steroidal anti-inflammatory drugs, including acetaminophen, sodium salicylate, naproxen and flurbiprofen, their elimination and inhibition ability of active oxygen, using of the electron spin resonance spin-trapping method and the horseradish peroxidase method. In this experiment as active oxygen models, superoxide was evolved from a hypoxanthine-xanthine oxidase reaction system, and hydrogen peroxide by the spontaneous dismutation reaction. The data here show that the amount of superoxide was reduced in the manner of concentration of non-steroidal anti-inflammatory drugs in the reaction. Kinetic studies for these reaction showed that acetaminophen and sodium salicylate reacted with superoxide competitively, whereas naproxen and flurbiprofen did not. Analysis of generation of hydrogen peroxide formed by the spontaneous dismutation of superoxide derived from the reaction system revealed that hydrogen peroxide was increased by acetaminophen and decreased by sodium salicylate, naproxen and flurbiprofen.