The iron-binding and hydroxyl radical scavenging action of anti-inflammatory drugs

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Abstract
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 1010 M−1 s−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.

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