Brain oxidative reactions and nitric oxide relation to the pro-and anticonvulsive activity of nitric oxide synthase modulators in pentylenetetrazol seizure model in mice

ABSTRACT

This study was carried out to investigate the possible effects and relation of brain levels of nitric oxide [NO], malondialdehyde [MDA] and glutathione [GSH], using the NO donor L-arginine [L-Arg, 75-1200 mg/kg] and the NO inhibitor, NG-nitro-L-arginine methyl ester [L- NAME, 25-150 mg/kg] and flunarizine [Flu, 10-40 mg/kg] and calcium channel blocker alone and in different combinations on pentylenetetrazol [PTZ] seizure severity, latency and threshold in mice. L-NAME decreased PTZ seizure threshold and caused a significant dose-dependent proconvulsant effect, which was partially antagonized by Flu [20 mg/kg]. Meanwhile, L-Arg produced a significant anti- convulsant activity and increased the FTZ threshold. Mortality was decreased by pretreatment with L-NAME, while all animals receiving protective doses of L-Arg did not show any mortality. In PTZ treated animals, MDA levels were increased, while GSH levels were decreased; this change was not related directly to the decreased brain NO levels by L-NAME. However, L-Arg significantly increased the formation of NO, which was associated with decreased lipid peroxidation. Moreover, it prevented the effect of PTZ on MDA and GSH. Flu failed to alter brain NO levels, but it caused about 10 folds increase in MDA and 2.5 folds increase in GSH when combined with L-Arg