ABSTRACT
To investigate a possible role of 8-isoprostaglandin F2alpha in inflammation, 8-isoprostaglandin F2alpha and prostaglandin E2 levels were determined by enzyme immunoassay (EIA) in carrageenan-induced air pouch model in rats. In this model, 8-isoprostaglandin F2alpha and prostaglandin E2 levels were found to be increased significantly. To evaluate whether this increase was due to the development of inflammation or solely to cyclooxygenase-2 induction, a lipopolysaccharide-induced air pouch model, in which only cyclooxygenase-2 induction occurs without inflammation, was used. In this model, 8-isoprostaglandin F2alpha was also found to be increased parallel to the increase in prostaglandin E2 level. Cyclooxygenase-dependent formation of 8-isoprostaglandin F2alpha was investigated in carrageenan-induced air pouch model by administrating nonselective cyclooxygenase inhibitor indomethacin, selective cyclooxygenase-1 inhibitor valeryl salicylate or selective cyclooxygenase-2 inhibitor SC-582368 (4-(5-(4-chlorophenyl)-3-3-trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonanmide) 1 h before carrageenan injection. All these inhibitors significantly inhibited the production of 8-isoprostaglandin F2alpha and prostaglandin E2. These findings show that 8-isoprostaglandin F2alpha can be formed in carrageenan-induced air pouch model in rats. The formation of 8-isoprostaglandin F2alpha in lipopolysaccharide-induced air pouch model and the inhibition of its production by various cyclooxygenase inhibitors provide evidence for cyclooxygenase-dependent formation of isoprostanes in this model.
