Lipid peroxidation in rat liver microsomes during naproxen metabolism

Naproxen, a non-steroidal anti-inflammatory drug, is known to be highly effective and relatively safe, but some side-effects in the liver have been reported. In the present study, the effect of naproxen metabolism on rat liver microsomes was studied by determining lipid peroxidation in terms of thiobarbituric acid reactive substances (TBA-RS), high molecular weight protein aggregates and fluorescent substances formed in the microsomal suspension containing naproxen, NADPH and MgCl2. Lipid peroxidation was found to occur at 10 mM naproxen. Production of chemiluminescence from the microsomal suspension was observed during naproxen metabolism. The time course of 6-demethyl-naproxen formation by O-demethylation of naproxen appeared to be comparable to that of the chemiluminescence production in their initial periods of production. These results suggest that the lipid peroxidation was provoked through the reactive oxygen species generated during the oxidative metabolism of naproxen.