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-argi nine (L-NARG), and a nitric oxide precursor, L-arginine (L-ARG), on th e lipid peroxidation induced by quinolinic acid (QUIN, an NMDA recepto r agonist), were both tested in synaptosomal fractions from whole rat brain. Baseline of lipid peroxidation was found at 2.43 +/- 0.24 fluor escence units/mg protein or 14.27 +/- 1.24 nmoles of TBARS/mg protein (100%). QUIN (100 mu M)-induced lipid peroxidation in synaptosomes (25 6% 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 mu M of L-NARG (74%, 58% , 56%, 48% and 48% vs. quinolinate value, respectively). Coincubation of synaptosomes with QUIN plus L-ARG (100 mu M), which alone resulted a potent Fro-oxidant (277% vs. control), increased the lipoperoxidativ e effect induced by QUIN alone in 120%, (290% vs. control). Synaptosom es simultaneously exposed to QUIN (100 mu M) plus L-ARG (100 mu M) plu s L-NARG (200 mu M) showed levels of lipid peroxidation similar to tho se of quinolinate alone. These findings suggest that nitric oxide may contribute to the oxidative damage induced in vitro by QUIN. (C) 1997 Elsevier Science Ireland Ltd.