Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity.
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.
Yildirim
Mehmet
M
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayis, 55139 Samsun, Turkey.
Ayyildiz
Mustafa
M
Agar
Erdal
E
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004569:Electroencephalography / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010406:Penicillins; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007191:Indazoles; D010406:Penicillins; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001205:Ascorbic Acid; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester