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.