F2-isoprostane induced prostaglandin formation in the rabbit

Abstract

F2-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF2α (a major F2-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F2α (PGF2α) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF2α was seen in both plasma and urine within a short interval after i.v. administration of 43 μg/kg of 8-iso-PGF2α to the rabbits. A successive but differential formation of PGF2α resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF2α, a major metabolite of primary PGF2α. Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF2α metabolite in plasma at 10 min and 12-fold increase in the urine at 30–60 after the i.v. administration of 8-iso-PGF2α was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF2α during oxidant stress induces prostaglandin formation presumbly through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.