A possible mechanism of naproxen-induced lipid peroxidation in rat liver microsomes

Previous papers from our laboratory report that naproxen and salicylic acid induced lipid peroxidation in rat liver microsomes, however, the mechanism is still unclear. In the present paper, ferrous iron release, nicotinamide -adenine dinucleotide phosphate reduced form (NADPH) oxidation and hydrogen peroxide (H2O2) formation have been measured to find out which mechanisms are involved in naproxen- and salicylic acid-induced lipid peroxidation. Wh ile the increase of ferrous iron release was observed with high concentrati ons of naproxen, salicylic acid did not stimulate ferrous iron release. Nei ther of these drugs stimulated NADPH oxidation and H2O2 formation. However hexobarbital and perfluorohexane, known as uncouplers of cytochrome P450, s timulated microsomal NADPH oxidation, O-2 consumption, H2O2 formation and w ater (H2O) formation involving four-electron oxidase reaction. These result s suggest that ferrous iron release contributes to naproxen-induced microso mal lipid peroxidation and that naproxen and salicylic acid are not uncoupl ers of cytochrome P450. Apparently H2O2 does not play an important role in naproxen- and salicylic acid-induced microsomal lipid peroxidation.