Metabolic activation of phenols by stimulated neutrophils: a concept for a selective type of anti-inflammatory drug.
Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent and selective inhibitor of neutrophil oxyradical production. The mechanism of action involves metabolic activation in a (myelo)-peroxidase-dependent reaction. The reaction product(s) prevent(s) the assembly of the superoxide anion-generating NADPH:O2 oxidoreductase by conjugation to essential thiol groups. Different neutrophil functions that are essential to their bactericidal activity, however, remain intact. When administered orally a potent anti-inflammatory activity was found in rats with experimentally induced local or systemic inflammation.
Hart
B A
BA
Department of Chronic Diseases, ITRI-TNO, Rijswijk, The Netherlands.
Simons
J M
JM
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010636:Phenols / Q000493:pharmacokinetics*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D016897:Respiratory Burst / Q000187:drug effects
D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010636:Phenols; D011809:Quinones; C056165:acetovanillone