The iron-binding and hydroxyl radical scavenging action of anti-inflammatory drugs.
1. Hydroxyl radicals (.OH) are thought to be generated at sites of inflammation and to contribute to tissue damage. All anti-inflammatory drugs tested were able to scavenge .OH generated in free solution at almost diffusion-controlled rates (rate constants about 10(10)M-1s-1). 2. Much .OH generation in vivo occurs at specific sites, where bound metal ions (such as Fe2+) react with H2O2 to produce .OH that immediately attacks the site. Only .OH scavengers that have sufficient metal-binding ability to withdraw metal ions from this site can protect against site-specific damage. 3. All anti-inflammatory drugs tested were able to protect against site-specific damage by .OH in a simple model system in vitro. Penicillamine, diclofenac sodium, piroxicam, azathioprine, primaquine, chloroquine and hydroxychloroquine were especially effective. 4. The ability of an anti-inflammatory drug to protect against .OH formation in vivo depends not only on its rate constant for reaction with .OH, but also on its metal-binding ability and on the geometry and redox potential of any metal complex formed.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D003855:Deoxyribose / Q000378:metabolism; D004492:Edetic Acid; D006900:Hydroxylation; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003855:Deoxyribose; D004492:Edetic Acid; D007501:Iron