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. While the increase of ferrous iron release was observed with high concentrations of naproxen, salicylic acid did not stimulate ferrous iron release. Neither of these drugs stimulated NADPH oxidation and H2O2 formation. However hexobarbital and perfluorohexane, known as uncouplers of cytochrome P450, stimulated microsomal NADPH oxidation, O2 consumption, H2O2 formation and water (H2O) formation involving four-electron oxidase reaction. These results suggest that ferrous iron release contributes to naproxen-induced microsomal lipid peroxidation and that naproxen and salicylic acid are not uncouplers of cytochrome P450. Apparently H2O2 does not play an important role in naproxen- and salicylic acid-induced microsomal lipid peroxidation.