Inhibition of polymorphonuclear leucocyte motility by benoxaprofen related to activation of cellular oxidative metabolism.
Incubation of human blood polymorphonuclear leucocytes (PMNL) with benoxaprofen at concentrations of greater than 1 X 10(-5)M caused inhibition of random and leucoattractant-induced migration of these cells in vitro. The drug at the same concentrations and in the absence of an added stimulant caused increased PMNL oxidative metabolism measured by chemiluminescence, hexose-monophosphate shunt activity and myeloperoxidase release. Furthermore benoxaprofen also induced PMNL auto-oxidation detected by cellular auto-iodination. Co-incubation of PMNL with the anti-oxidants ascorbate or levamisole prevented benoxaprofen-mediated inhibition of PMNL migration and cellular auto-oxidation. The drug per se was not an oxidising agent and its inhibitory effects on PMNL motility were dependent upon intact cellular oxidative metabolism. The inhibitory effects of benoxaprofen on PMNL migration in vitro are caused by the proxidant activity of the drug.
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology*
D000975:Antioxidants; D011422:Propionates; C011677:benoxaprofen; D001205:Ascorbic Acid