Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: Determination by electron spin resonance using the spin trap method

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to man age pain, are known to inhibit cyclooxygenase, but details of the mechanism s of NSAID action remain unclear. We investigated the ability of three NSAI Ds (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free r adicals. Superoxide scavenging activity of these NSAIDs was measured in vit ro by electron spin resonance spectrometry using 5,5-dimethyl-pyrroline-1-p yroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cycloosygenase inhibitors, indomethacin (3 mmol) and loxop rofen (3 mmol). The electron spin resonance study also demonstrated that th e formation of superoxide-DMPO spin adduct was strongly inhibited by a sele ctive cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent ma nner. These results indicate that NSAIDs, including indomethacin, loxoprofe n, and etodolac, have direct superoxide scavenging activity.