title: Homocysteine thiolactone-induced seizures in adult rats are aggravated by inhibition of inducible nitric oxide synthase.
abstract: Homocysteine and its metabolites (homocysteine thiolactone (HT)) induce seizures via different but still not well-known mechanisms. The role of nitric oxide (NO) in epileptogenesis is highly contradictory and depends on, among other factors, the source of NO production. The aim of the present study was to examine the effects of aminoguanidine, selective inhibitor of inducible NO synthase (iNOS), on HT-induced seizures. Aminoguanidine (50, 75, and 100 mg/kg, intraperitoneally (i.p.)) was injected to rats 30 min prior to inducing HT (5.5 mmol/kg, i.p.). Seizure behavior was assessed by seizure incidence, latency time to first seizure onset, number of seizure episodes, and their severity during observational period of 90 min. Number and duration of spike and wave discharges (SWDs) were determined in electroencephalogram (EEG). Seizure latency time was significantly shortened, while seizure incidence, number, and duration of HT-induced SWD in EEG significantly increased in rats receiving aminoguanidine 100 mg/kg before subconvulsive dose of HT. Aminoguanidine in a dose-dependent manner also significantly increased the number of seizure episodes induced by HT and their severity. It could be concluded that iNOS inhibitor (aminoguanidine) markedly aggravates behavioral and EEG manifestations of HT-induced seizures in rats, showing functional involvement of iNOS in homocysteine convulsive mechanisms.
authors.affiliation: 1Laboratory of Neurophysiology, Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Hrnčić
authors.forename: A
authors.initials: A
authors.lastname: Rašić-Marković
authors.forename: D
authors.initials: D
authors.lastname: Macut
authors.forename: V
authors.initials: V
authors.lastname: Šušić
authors.forename: D
authors.initials: D
authors.lastname: Djuric
authors.forename: O
authors.initials: O
authors.lastname: Stanojlović
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004569:Electroencephalography; D006710:Homocysteine / Q000009:adverse effects / Q000031:analogs & derivatives*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology
chemical_list: D006710:Homocysteine; C007957:homocysteine thiolactone; D052247:Nitric Oxide Synthase Type II
keywords: EEG; aminoguanidine; homocysteine; iNOS inhibition; rats; seizures