Hydroxyl Radical Scavenging Activity of Nonsteroidal Anti-Inflammatory Drugs

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Abstract
The hydroxyl radical (.OH) -scavenging activity of d-2–[4–(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a novel nonsteroidal anti-inflammatory drug (NSAID), and that of several other NSAIDs were investigated by the hyaluronic acid (HA) degradation method and the electron spin resonance (ESR) spin-trapping technique. The superoxide anion (O2) -scavenging activity of M-5011 was also measured by the ESR technique. (1) M-5011 and the other NSAIDs examined inhibited the degradation of HA induced by the Fenton reaction system in a dose-dependent manner. (2) M-5011 and the other NSAIDs scavenged OH directly in a dose-dependent manner. (3) M-5011 was the most potent drug among the NSAIDs tested regarding the scavenging activity of OH as follows; M-5011 > indomethacin > ketoprofen = suprofen > aspirin. The OH-scavenging activity of M-5011 was potent in comparison with that of oxidized glutathione (GSSG), an endogenous OH scavenger. (4) M-5011 did not scavenge O2; nor did GSSG. These results suggest that M-5011 acts as a scavenger of OH at sites with inflammatory lesions.