Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity

This report investigates the plasma and/or urinary levels of 8-iso-PGF(2 alpha), a nonenzymatic, and 15-ketodihydro-PGF(2 alpha) a cyclooxygenase catalyzed oxidation product of arachidonic acid in experimental hepatotoxicity in rats. The study was undertaken to evaluate oxidative injury-induced inflammation as a consequence of cyclooxygenase induction. A significant and immediate increase of 8-iso-PGF(2 alpha) in both plasma and urine after CCl4 administration indicates an oxidative injury during acute hepatotoxicity in rats. The inflammatory response index was determined by measuring 15-keto-dihydro-PGF(2 alpha) levels in plasma which increased significantly 9-fold at 4 h after the administration of CCl4. The oxidative injury index, 8-iso-PGF(2 alpha), in both plasma and urine increased 17- and 53-fold, respectively. Six hours later the levels of 15-ketodihydro-PGF(2 alpha) in plasma remained high (5-fold increase) when 8-iso-PGF(2 alpha) levels in plasma and urine elevated to 7- and 87-fold, respectively. Thus, cyclooxygenase and free radical-catalyzed oxidation of arachidonic acid are well involved during CCl4-induced hepatotoxicity, Cyclooxygenase-dependent inflammatory response through PGF(2 alpha) formation in CCl4-induced hepatotoxicity may possibly be a secondary effect to oxidative injury and a conceivable link between inflammatory response and oxidative injury. (C) 1999 Academic Press.