Polymorphonuclear leukocytes activation: in vitro modulation by 6-methoxy-2-naphthylacetic acid, the major active metabolite of nabumetone.
Reported here are the results of a study carried out in order to assess the possible influence of the major circulating active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, on some aspects of polymorphonuclear leukocytes activation. The action of 6-methoxy-2-naphthylacetic acid was tested on the following features of polymorphonuclear leukocytes activation: reactive oxygen species production in polymorphonuclear leukocytes stimulated with different agonists, reactive oxygen species production in polymorphonuclear leukocytes treated with pertussis toxin, NADPH-oxidase activity. The findings showed that 6-methoxy-2-naphthylacetic acid decreased reactive oxygen species production in polymorphonuclear leukocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and opsonized zymosan, but failed to provoke a decrease of reactive oxygen species production when the cells were stimulated with calcium ionophore A23187. Moreover, 6-methoxy-2-naphthylacetic acid did not influence the transduction of the signal following the binding of stimuli to membrane receptors, and NADPH-oxidase activity. Finally, our findings showed that 6-methoxy-2-naphthyl acetic acid had no scavenger effect on reactive oxygen species production.
Allegrezza-Giulietti
A
A
Institute of Rheumatology, Faculty of Medicine, University of Ancona, Italy.
Serretti
R
R
Peroni
M
M
Cervini
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D002074:Butanones / Q000378:metabolism*; D016166:Free Radical Scavengers; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D016166:Free Radical Scavengers; D009280:Naphthaleneacetic Acids; D010566:Virulence Factors, Bordetella; C044612:6-methoxy-2-naphthylacetic acid; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D037342:Pertussis Toxin; D000077430:Nabumetone