Effects of N omega-nitro-L-arginine and L-arginine on quinolinic acid-induced lipid peroxidation

The effects of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NARG), and a nitric oxide precursor, L-arginine (L-ARG), on the lipid peroxidation induced by quinolinic acid (QUIN, an NMDA receptor agonist), were both tested in synaptosomal fractions from whole rat brain. Baseline of lipid peroxidation was found at 2.43 +/- 0.24 fluorescence units/mg protein or 14.27 +/- 1.24 nmoles of TBARS/mg protein (100%). QUIN (100 microM)-induced lipid peroxidation in synaptosomes (256% and 166% vs. control, as measured by lipid fluorescent products and thiobarbituric acid-reactive substances, respectively) was inhibited by concentrations of 10, 40, 100, 200 and 400 microM of L-NARG (74%, 58%, 56%, 48% and 48% vs. quinolinate value, respectively). Coincubation of synaptosomes with QUIN plus L-ARG (100 microM), which alone resulted a potent pro-oxidant (277% vs. control), increased the lipoperoxidative effect induced by QUIN alone in 120% (290% vs. control). Synaptosomes simultaneously exposed to QUIN (100 microM) plus L-ARG (100 microM) plus L-NARG (200 microM) showed levels of lipid peroxidation similar to those of quinolinate alone. These findings suggest that nitric oxide may contribute to the oxidative damage induced in vitro by QUIN.