EFFECTS OF ORPANOXIN ON ARACHIDONIC ACID METABOLISM OF HUMAN POLYMORPHONUCLEAR LEUCOCYTES AND PLATELETS IN VITRO

Abstract

1. The effect of orpanoxin, a nonsteroidal anti-inflammatory drug, on cyclo-oxygenase and lipoxygenase activity in human polymorphonuclear leucocytes (PMNL) and platelets was studied ex vivo to see if lipoxygenase inhibition contributed to orpanoxin's mechanism of action. 2. In PMNL, orpanoxin (50, 100, and 200 mumols/l), like indomethacin (100 mumols/l), had little effect on synthesis of leukotriene B4 or 5S-hydroxy-6-trans,8,11,14-cis-eicosatetraenoic acid. BW755c at 100 mumols/l inhibited synthesis of both. 3. In PLT, orpanoxin (100 mumols/l) inhibited formation of cyclo-oxygenase products (thromboxanes, prostaglandins, and 12-L-hydroxy-5,8,10-heptadecatrienoic acid) and increased synthesis of the lipoxygenase product, 12S-hydroxy-5,8-cis,10-trans,14-cis-eicosatetraenoic acid. Effects of indomethacin (100 mumols/l) and benoxaprofen (100 mumols/l) in platelets were qualitatively similar to those of orpanoxin. 4. These results indicate that the discrepancy between the low potency of orpanoxin in inhibiting bovine seminal vesicle cyclo-oxygenase in vitro and its high potency as an anti-inflammatory agent in vivo is not explained by its having an additional lipoxygenase inhibitory mechanism.