Comparison of the pro-oxidative interactions of flunoxaprofen and benoxaprofen with human polymorphonuclear leucocytes in vitro.
At concentrations of 3.75 micrograms/ml and greater the non-steroidal anti-inflammatory drugs, benoxaprofen and to a lesser extent flunoxaprofen, caused dose-related spontaneous activation of both luminol- and lucigenin-enhanced chemiluminescence in human polymorphonuclear leucocytes (PMNL) in vitro. Flunoxaprofen- and benoxaprofen-mediated activation of oxidant release by PMNL was increased by UV-radiation. Pre-incubation of PMNL with sub-stimulatory concentrations of both drugs greatly enhanced the release of reactive oxygen species on subsequent exposure of the cells to various standard stimuli of membrane-associated oxidative metabolism. The protein kinase C inhibitor, H-7, and the phospholipase A2 inhibitor, BPB, both prevented drug-mediated activation of superoxide generation by PMNL. Flunoxaprofen-mediated stimulation of PMNL membrane-associated oxidative metabolism is, like benoxaprofen, due to apparent activation of protein kinase C. These findings establish the pro-oxidative properties of flunoxaprofen.
Van Rensburg
A J
AJ
Department of Immunology, University of Pretoria, Republic of South Africa.
Theron
A J
AJ
Anderson
R
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000098:Acetophenones / Q000494:pharmacology; D000166:Acridines / Q000494:pharmacology; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001583:Benzoxazoles / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000494:pharmacology; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010879:Piperazines / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D013482:Superoxide Dismutase / Q000494:pharmacology; D014466:Ultraviolet Rays
D000098:Acetophenones; D000166:Acridines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; D007202:Indicators and Reagents; D007546:Isoquinolines; D016877:Oxidants; D010879:Piperazines; D011422:Propionates; D047428:Protein Kinase Inhibitors; C011677:benoxaprofen; C033472:10,10'-dimethyl-9,9'-biacridinium; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013482:Superoxide Dismutase; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; C045356:flunoxaprofen