Ascorbic acid and
nitric oxide are known to play important roles in
epilepsy. The aim of present study was to identify the involvement of
nitric oxide (NO) in the
anticonvulsant effects of
ascorbic acid on
penicillin-induced epileptiform activity in rats. Intracortical injection of
penicillin (500, International Units (IU)) into the left sensorimotor cortex induced epileptiform activity within 2-5 min. Thirty minutes after
penicillin injection,
nitric oxide synthase (NOS) inhibitor,
N(G)-nitro-l-arginine methyl ester (
l-NAME, 100mg/kg),
neuronal nitric oxide synthase (nNOS) inhibitor
7-nitroindazole (7-NI, 40 mg/kg), NO substrate,
l-arginine (500 mg/kg) were administered with the most effective dose of
ascorbic acid (100 mg/kg) intraperitoneally (i.p.). The administration of
l-arginine significantly decreased the frequency of epileptiform activity while administration of
l-NAME did not influence the mean frequency of epileptiform activity. Injection of 7-NI decreased the mean frequency of epileptiform activity but did not influence amplitude.
Ascorbic acid decreased both the mean frequency and amplitude of
penicillin-induced epileptiform activity in rats. The application of
l-NAME partially and temporarily reversed the
anticonvulsant effects of
ascorbic acid. The results support the hypothesis of neuro-protective role for NO and
ascorbic acid. The protective effect of
ascorbic acid against epileptiform activity was partially and temporarily reversed by nonspecific
nitric oxide synthase inhibitor
l-NAME, but not selective
neuronal nitric oxide synthase inhibitor 7-NI, indicating that
ascorbic acid needs endothelial-NOS/NO route to decrease
penicillin-induced epileptiform activity.