The role of nitric oxide in the anticonvulsant effects of pyridoxine on penicillin-induced epileptiform activity in rats.
The present study was conducted to identify the role of nitric oxide (NO) in the anticonvulsant effects of pyridoxine hydrochloride on penicillin-induced epileptiform activity in rats. A single microinjection of penicillin (500 units) into the left sensorimotor cortex induced epileptiform activity within 2-4 min, progressing to full seizure activity lasting about 3-5h. Thirty minutes after penicillin injection, 20, 40, 80, and 160 mg/kg of pyridoxine hydrochloride was administered intraperitoneally (i.p.). Pyridoxine significantly reduced the frequency of penicillin-induced epileptiform activity. A low dose of pyridoxine (40 mg/kg) was the most effective in reducing both the frequency and amplitude of epileptiform activity. The effect of systemic administration of nitric oxide synthase (NOS) inhibitors, non-selective N(G)-nitro-L-arginine methyl ester (L-NAME), selective neuronal NOS inhibitor, 7-nitroindazole (7-NI) and NO substrate, L-arginine on anticonvulsive effects of pyridoxine was investigated. The administration of L-arginine (500 mg/kg, i.p.) and 7-NI (25 and 50 mg/kg, i.p.) significantly decreased the frequency of epileptiform electrocorticographical (ECoG) activity while administration of L-NAME (60 mg/kg, i.p.) and the inactive form of arginine (D-arginine) did not influence it. The administration of L-NAME (60 mg/kg, i.p.) 15 min before pyridoxine (40 mg/kg i.p.) application reversed the anticonvulsant effects of pyridoxine whereas 7-NI (25 and 50 mg/kg, i.p.) did not influence it. The same dose of its inactive enantiomer N(G)-nitro-D-arginine methyl ester (d-NAME) failed to reverse the anticonvulsant effects of pyridoxine. The administration of L-arginine (500 mg/kg, i.p.) did not affect the frequency of epileptiform ECoG activity in the pyridoxine administered group. L-arginine did not reverse the anticonvulsant effect of 7-NI in the penicillin and pyridoxine administered groups. The results of present study indicate that the inhibitory effect on the anticonvulsant activity of pyridoxine against penicillin-induced epileptiform activity was produced by L-NAME, not by 7-NI, and is probably not related to the decrease of NOS activity in the brain.
Bosnak
Mehmet
M
Department of Physiology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
Ayyildiz
Mustafa
M
Yildirim
Mehmet
M
Agar
Erdal
E
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010406:Penicillins; D011736:Pyridoxine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D007191:Indazoles; D010406:Penicillins; D009569:Nitric Oxide; D001120:Arginine; D011736:Pyridoxine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester