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Öğe Anticonvulsant effect of carnosine on penicillin-induced epileptiform activity in rats(Elsevier, 2008) Kozan, Ramazan; Sefil, Fatih; Bagirici, FarukCarnosine is a compound of naturally-occurring dipeptide that synthesized by the carnosine synthetase from beta-alanine and L-histidine. Recent reports claim that carnosine plays an important role in the control of epilepsy but its involvement in anticonvulsant functions remains unknown. In this study, we investigated the effects of carnosine in a rat model of epilepsy using the intracortical penicillin injection method. Thirty minutes after penicillin injection, the doses of 125, 250, 500, 1000 mg/kg carnosine and 90 min before penicillin injection the dose of 500 mg/kg carnosine were administered intraperitoneally. The epileptiform activity was verified by electrocorticographic (ECoG) recordings. The mean spike frequency of penicillin-induced epileptiform activity was significantly decreased in all carnosine-treated rats when compared with those of penicillin-injected. The dose of 500 mg/kg for carnosine treated and pretreated rats was found to be the most effective dose in reducing the frequency of penicillin-induced epileptiform activity. There was no significant difference in the mean onset of epileptiform activity between penicillin and 500 mg/kg camosine pretreated groups. These findings indicate that carnosine has an anticonvulsant effect on penicillin-induced epilepsy in rats. Thus, our data support the hypothesis that carnosine may be a potential anticonvulsant drug for clinical therapy of epilepsy in the future. (C) 2008 Elsevier B.V. All rights reserved.Öğe Effect of levetiracetam on penicillin induced epileptic activity in rats(Nencki Inst Experimental Biology, 2014) Arik, Aliye Erguvan; Bagirici, Faruk; Sefil, Fatih; Marangoz, CaferThe aim of this study was to investigate the effects of levetiracetam (LEV) on penicillin- induced epileptiform activity in rats. Penicillin was applied intracerebroventricularly (icy) at a dose of 500 IU to induce epileptiform activity. LEV was given intraperitoneally (ip) at doses of 20, 40, 80 mg/kg before penicillin injection. This agent reduced epileptiform activity by decreasing spike frequencies. The mean spike frequencies decreased significantly in all the LEV treated groups. There was no significant change in the spike amplitudes of the LEV groups compared with the control group. 40 mg/kg of LEV was determined as the most effective dose on reducing epileptiform activity. The results of this study suggest that LEV is an effective antiepileptic agent in penicillin-induced epilepsy.Öğe Influence of carbenoxolone on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats(Nencki Inst Experimental Biology, 2012) Sefil, Fatih; Bagirici, Faruk; Acar, M. Dilek; Marangoz, CaferAbnormal synchronized neuronal discharges mediated by gap junctions have an important role in epileptic seizures. The analysis of anticonvulsant drugs acting on gap junctions is still a priority in epilepsy research. Therefore, the present study was designed to investigate the effect of carbenoxolone, a gap junction blocker, on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats. Male Wistar albino rats, 14 weeks of age, were used. In the first step of the study, animals were given PTZ 35 mg/kg intraperitoneally (i.p.) three times a week until kindling was produced. Then, indwelling screw electrodes - allowing EEG monitoring of conscious rats - were implanted into the crania of the kindled rats. In this way, we were able to record EEG activity and evaluate seizure stage at the same time. In the second step of the study, the interaction between carbenoxolone (40 mg/kg i.p.) and phenytoin (60 mg/kg, i.p.) was investigated. The data analysis was performed using a one-way ANOVA with LSD post-hoc test. Total spike number and the generalized seizure duration were reduced in the carbenoxolone treated group compared to the PTZ group. Phenytoin decreased generalized seizure duration, total spike number and seizure severity score. Carbenoxolone and phenytoin have anti-seizure effects in PTZ kindled rats. There was no significant difference between the carbenoxolone + phenytoin combination and phenytoin in terms of generalized seizure duration, total spike number and seizure stage. The results indicate that carbenoxolone combined with phenytoin is not more effective than the use of these drugs alone.Öğe Inhibition of neuronal nitric oxide synthase prevents iron-induced cerebellar Purkinje cell loss in the rat(Nencki Inst Experimental Biology, 2008) Gulturk, Sefa; Kozan, Ramazan; Bostanci, M. Omer; Sefil, Fatih; Bagirici, FarukIron plays an important role in maintaining normal. brain function. However, in many neurodegenerative diseases abnormal iron accumulation in specific brain regions has been consistently reported. In this study, we investigated the neurotoxic effect of the intracerebroventricularly injected iron on the cerebellar Purkinje cells in the rat and the role of nitric oxide (NO) in this process. The role of NO in rats administered iron (FeCl(3)6H(2)O) was examined with the use of a donor of NO, L-arginine (L-Arg), and a central selective inhibitor of NO synthase, 7-nitroindazole (7-NI). For this reason, rats were divided into 5 groups: control, iron-injected, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI. Means (value standard deviation) of the total numbers of Purkinje cells in the cerebellum were estimated as 337 +/- 23, 209 +/- 16, 167 +/- 19, 305 26, and 265 +/- 14 thousands in the control, iron, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI groups, respectively. Iron treatment alone and the combination of iron and L-Arg caused a significant reduction in the total number of cerebellar Purkinje cells. Therefore, L-Arg increased the Purkinje cell loss induced by treatment with iron. These data show that inhibition of the neuronal NOS by 7-NI can prevent some of the deleterious effects of iron on cerebellar Purkinje cells. Presence of L-arginine decreased the neuroprotective effect of 7-NI.Öğe Interaction between carbenoxolone and valproic acid on pentylenetetrazole kindling model of epilepsy(E-Century Publishing Corp, 2015) Sefil, Fatih; Arik, Aliye E.; Acar, Meryem D.; Bostanci, Mehmet O.; Bagirici, Faruk; Kozan, RamazanGap junctions play an important role in the synchronized neuronal discharges. The main reason of the epileptic seizures is disruption of this synchronization. Therefore, the aim of the present study is to explore the combination valproic acid with carbenoxolone in pentylenetetrazole-kindled rats. In the first set of experiments, pentylenetetrazole (35 mg/kg intraperitoneally was administered to the rats to produce the kindling and then permanent screw electrodes to record electroencephalographic signals. The kindled rats were divided into six groups. While electroencephalographic recordings received from animals, behavioral evaluation was done by an observer. The data analysis was performed using T test and Mann-Whitney U tests. The dose of 40 mg/kg carbenoxolone was the most effective in carbenoxolone treatment groups. It prevented generalized seizures by 50%, reduced seizure stage, seizure duration and spike frequency. There was no significant difference between carbenoxolone-valproic acid combination and valproic acid on any seizure parameters. The current study is the first study which shows the interaction of carbenoxolone with valproic acid in pentylenetetrazole kindling model. As a result, carbenoxolone-valproic acid combination was not more effective than the standalone use of these drugs.Öğe Iron-Induced Cerebellar Purkinje Cell Loss Is Ameliorated by Flunarizine(Tubitak Scientific & Technological Research Council Turkey, 2009) Kozan, Ramazan; Bostanci, M. Oemer; Nacar, Tuncer; Aslan, Ali; Bagirici, FarukAim: In this study, we investigated the effect of intracerebroventricular-injected iron neurotoxicity on the total number of cerebellar Purkiinje cells in rats and the possible neuroprotective effect of flunarizine, a piperazine-derived calcium channel blocker. Materials and Methods: Rats were divided into four groups: control, flunarizine. iron, and iron + flunarizine groups. Rats in the iron and iron + flunarizine groups received intracerebro-ventricular iron (FeCl36H2O. 200 mM, 2.5 mu l), while those in flunarizine and iron + flunarizine groups were intraperitoneally injected with flunarizine (10 mg/kg/day) once a day after the operation for 10 days. After 10 days, all rats were perfused intracardially and then sacrificed. Brain tissues were removed and standard histological techniques were performed. The total numbers of Purkinje cells were estimated using unbiased stereological techniques. Results: Means of the total numbers of Purkinje cells in the cerebellum were estimated as 310441 +/- 6558, 298658 +/- 9636, 200201 +/- 6822 and 282658 +/- 6327 in the control, flunarizine, iron, and iron + flunarizine groups. respectively. Comparison between iron and iron + flunarizine groups revealed that flunarizine significantly attenuates the iron-induced neuron loss from 35.5% to 8.9% (P < 0.05). Conclusions: Findings of the present study suggest that flunarizine has a neuroprotective effect on iron-induced Purkinje cell loss in the rat cerebellum via blocking influx of calcium ions into neurons.