The role of nitric oxide in homocysteine thiolactone-induced seizures in adult rats.
The role of NO in epileptogenesis has been studied in different experimental models, and the reported results have been highly contradictory. The current study aimed to determine the role of NO in mechanisms of D: ,L: -homocysteine-thiolactone (H) induced seizures by testing the action of L: -arginine (NO precursor) and L: -NAME (NOS inhibitor) on behavioral and electroencephalographic (EEG) manifestations of H-induced seizures. The same holds true with the brain Na(+)/K(+)- and Mg(2+)-ATPase activity in adult male Wistar rats. We showed that the pretreatment with L: -arginine (300, 600 and 800 mg/kg, i.p.) in a dose-dependent manner significantly decreased lethality, seizure incidence and a number of seizure episodes and prolonged latency time to the first seizure elicited by a convulsive dose of H (8 mmol/kg, i.p.). L: -Arginine (800 mg/kg) completely reversed the inhibitory effect of H on the Na(+)/K(+)-ATPase activity in the hippocampus, the cortex and the brain stem and decreased the H-induced spike-and- wave discharges (SWD) formation in EEG. On the other hand, pretreatment with L: -NAME (200, 500 and 700 mg/kg, i.p.) potentiated a subconvulsive dose of H (5.5 mmol/kg, i.p) by increasing incidence and severity determined by a descriptive-rating scale (0-4) and shortening the latency time to the first seizure. The L: -NAME reversed H-induced alterations in the Na(+)/K(+)-ATPase activity in the cortex and the brain stem but not in the hippocampus. At last, the potentiated SWD appearance in EEG and an increased number of lethal outcomes occurred. In the present work, the modulation of NO levels, with the NO precursor and NOS inhibitor, was shed more light on its mechanism of action and answered the question whether NO could be included in the list of anticonvulsant agents in the D: ,L: -homocysteine thiolactone experimental model of seizures in adult rats.
Hrncić
Dragan
D
Laboratory of Neurophysiology, Institute of Medical Physiology Richard Burian, School of Medicine, University of Belgrade, Visegradska 26/II, 11000, Belgrade, Serbia.
Rasić-Marković
Aleksandra
A
Krstić
Danijela
D
Macut
Djuro
D
Djuric
Dragan
D
Stanojlović
Olivera
O
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D011837:Radiation-Protective Agents; D006710:Homocysteine; D009569:Nitric Oxide; C007957:homocysteine thiolactone; D000254:Sodium-Potassium-Exchanging ATPase; D019331:NG-Nitroarginine Methyl Ester