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Öğe Determination of Vascular Endothelial Growth Factor (VEGF) and Tie-2 Levels in Patients with Primary Hypertension(ELSEVIER SCIENCE INC, 2013) Filiz, Ahmet Kemal; Gunes, Hakan; Ozdemir, Ercan; Gunes, Handan; Yilmaz, Mehmet Birhan…Öğe Farelerde Pentilentetrazol ile Oluşturulan Epileptik Nöbetler Üzerine Anakinra’nın Etkisinin Araştırılması(2021) Filiz, Ahmet Kemal; Karabulut, SebahattinAmaç: Beyinde gama aminobutirik asit (GABA) ve glutamat arasındaki dengenin bozulması, nöbet oluşumuna ve epileptogenezekatkı sağlayan önemli faktörlerden biridir. Bu çalışmanın amacı, anakinra ön tedavisinin pentilentetrazol (PTZ) ile oluşturulan nöbetmodelinde kortikal ve hipokampal GABA ve glutamat seviyeleri üzerine etkisinin olup olmadığını belirlemektir.Araçlar ve Yöntem: Çalışmada 18 adet BALB-c türü fare Kontrol, PTZ ve Anakinra grupları şeklinde 3 gruba ayrıldı. Nöbetleribaşlatmak için 60 mg/kg dozda PTZ enjeksiyonu farelere intraperitonal olarak uygulandı. Anakinra grubuna PTZ enjeksiyonundan 30dakika önce intraperitonal olarak anakinra (100 mg/kg) uygulandı. Hayvanların kortikal ve hipokampal GABA ve glutamat düzeyleriEnzyme Linked Immunosorbent Assay (ELISA) yöntemi kullanılarak ölçüldü.Bulgular: PTZ'nin neden olduğu nöbetler, hipokampusta glutamat seviyesini artırırken (p<0.001), GABA düzeyinde azalmaya yolaçtı (p<0.05). PTZ tedavisi kortikal glutamat seviyesini arttırdı (p<0.05). Anakinra ile ön tedavi hipokampusta glutamat düzeyiniazaltırken (p<0.001), GABA düzeyinde artışa yol açtı (p<0.01). Ayrıca anakinra ön tedavisi kortikal glutamat seviyesini azaltırken(p<0.05), GABA düzeyinde artışla sonuçlandı (p<0.001).Sonuç: PTZ'nin neden olduğu nöbetler beyinde GABA düzeyinin azalmasına ve glutamat seviyesinin artışına neden olmaktadır. PTZenjeksiyonu öncesinde anakinra tedavisi farelerin beyinlerinde uyarılma lehine bozulmuş GABA/Glutamat dengesizliğini iyileştirmektedirÖğe Farelerde Pentilentetrazol ile Oluşturulan Epileptik Nöbetler Üzerine Anakinra’nın Etkisinin Araştırılması(Kırşehir Ahi Evran Üniversitesi, 2021) Filiz, Ahmet Kemal; Karabulut, SebahattinAmaç: Beyinde gama aminobutirik asit (GABA) ve glutamat arasındaki dengenin bozulması, nöbet oluşumuna ve epileptogeneze katkı sağlayan önemli faktörlerden biridir. Bu çalışmanın amacı, anakinra ön tedavisinin pentilentetrazol (PTZ) ile oluşturulan nöbet modelinde kortikal ve hipokampal GABA ve glutamat seviyeleri üzerine etkisinin olup olmadığını belirlemektir.Araçlar ve Yöntem: Çalışmada 18 adet BALB-c türü fare Kontrol, PTZ ve Anakinra grupları şeklinde 3 gruba ayrıldı. Nöbetleri başlatmak için 60 mg/kg dozda PTZ enjeksiyonu farelere intraperitonal olarak uygulandı. Anakinra grubuna PTZ enjeksiyonundan 30 dakika önce intraperitonal olarak anakinra (100 mg/kg) uygulandı. Hayvanların kortikal ve hipokampal GABA ve glutamat düzeyleri Enzyme Linked Immunosorbent Assay (ELISA) yöntemi kullanılarak ölçüldü.Bulgular: PTZ'nin neden olduğu nöbetler, hipokampusta glutamat seviyesini artırırken (p<0.001), GABA düzeyinde azalmaya yol açtı (p<0.05). PTZ tedavisi kortikal glutamat seviyesini arttırdı (p<0.05). Anakinra ile ön tedavi hipokampusta glutamat düzeyini azaltırken (p<0.001), GABA düzeyinde artışa yol açtı (p<0.01). Ayrıca anakinra ön tedavisi kortikal glutamat seviyesini azaltırken (p<0.05), GABA düzeyinde artışla sonuçlandı (p<0.001).Sonuç: PTZ'nin neden olduğu nöbetler beyinde GABA düzeyinin azalmasına ve glutamat seviyesinin artışına neden olmaktadır. PTZ enjeksiyonu öncesinde anakinra tedavisi farelerin beyinlerinde uyarılma lehine bozulmuş GABA/Glutamat dengesizliğini iyileştir-mektedir.Öğe Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats(Canadian Science Publishing, 2021) Baser, Tayfun; Ozdemir, Ercan; Filiz, Ahmet Kemal; Taskiran, Ahmet Sevki; Gursoy, SinanGhrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [D-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg.kg(-1)), [D-Lys3]-GHRP-6 (10 mg.kg(-1)), and morphine (5 mg.kg(-1)) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [D-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In condusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.Öğe İnterlökin - 1 Reseptör Antagonisti Ve RNA Polimeraz İnhibitörünün Hipokampal Hücre Hattında Nörodejenerasyon Üzerine Etkilerinin İncelenmesi(Sivas Cumhuriyet Üniversitesi, 2024) Şahin, Mehtap; Filiz, Ahmet KemalAmaç: Bu çalışmada bir RNA polimeraz inhibitörü; favipravirin ve İnterlökin-1 reseptörü antagonisti anakinranın, hipokampal hücrelerde glutamatla oluşturulacak sitotoksisite üzerine anti-nörodejeneratif etkilerinin araştırılması amaçlandı. Glutamata olan aşırı duyarlılığı nedeniyle HT22 hücre hattı kullanıldı. Yöntem: Kontrol, glutamat (10 mM), anakinra (1,10,25,50,100 μg), favipravir (1,10,25,50,100 μg) ve anakinra+favipravir hücre grupları oluşturuldu Kontrol grubuna herhangi bir tedavi uygulanmadı. Glutamat ile indüklenen grubun hücrelerine 24 saat boyunca 10 mM glutamat verildi. Anakinra grubundaki hücrelere 24 saat boyunca çeşitli konsantrasyonlarda (1,10, 25, 50, 100 μg) anakinra verildi. Favipravir grubundaki hücrelere 24 saat boyunca çeşitli konsantrasyonlarda (1,10,25,50,100 μg) favipravir verildi. Anakinra+glutamat grubundaki hücreler, 1 saat boyunca farklı konsantrasyonlarda (1,10,25,50,100 μg) anakinra ile ön işleme tabi tutuldu ve ardından 24 saat boyunca 10 mM glutamat uygulandı. Favipiravir+glutamat grubundaki hücreler, 1 saat boyunca farklı konsantrasyonlarda (1, 10, 25, 50,100 μg) favipiravir ile ön işleme tabi tutuldu ve ardından 24 saat boyunca 10 mM glutamat uygulandı. Ardından etkili dozlar belirlenerek anakinra+favipiavir+glutamattan oluşan kombinasyonları uygulandı. Bulgular: Yalnızca favipravirin farklı dozlarının uygulanmasınında viabilite üzerinde herhangi bir etkisi gözlenmedi (p< 0.01 kontrole göre). 100 μg anakinra uygulanan grupta hücre canlılığının diğer gruplara göre daha fazla olduğu gözlendi (pÖğe Involvement of nitric oxide pathway in the acute anticonvulsant effect of salmon calcitonin in rats(Elsevier, 2022) Filiz, Ahmet Kemal; Karabulut, SebahattinEpilepsy is a chronic neurological disease that is thought to affect up to 1% of the world's population. Evidence suggests that salmon calcitonin (sCT) has positive effects on epileptic seizures and epileptogenesis. However, it remains unknown that whether nitric oxide (NO) pathway contributed to this antiepileptic effect of sCT. We have used the pentylenetetrazole (PTZ)-induced seizure rat model to identify the effect of sCT on seizure score, seizure-induced cognitive deficit, and the NO pathway in the brain. We found that sCT increases the first myoclonic jerk (FMJ), decreased Racine's convulsion scale (RCS), and abates seizure-induced cognitive impairment. We further demonstrated that sCT attenuated the abnormal increase of NO in the brain. These results revealed that sCT exerts an antiepileptic effect by modulating the NO pathway in the brain.Öğe Mechanism of anti-cancer effect of ?-glucan on SH-SY5Y cell line(Bangladesh Pharmacological Soc, 2021) Filiz, Ahmet Kemal; Joha, Ziad; Yulak, FatihAnti-cancer property of fungi derived 13-glucan (Lentinula edodes) on several cancer cell lines have been reported. In this work, the SH-SY5Y cell lines were treated with various concentrations of 13-glucan (62.5, 125, 250 and 500 pg/mL) and the viability of the cells was tested using the XTT assay after 24 hours. Cleaved PARP, BCL-2, 8-hydroxy-desoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant levels in the cells were measured by commercial kits. 13-Glucan significantly decreased the cell viability in SH-SY5Y cells. ELISA tests demonstrated that 13-glucan therapy dramatically increased 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, total oxidant. However, 13-glucan treatment did not change the BCL-2 protein level. Altogether, 13-glucan caused significant cytotoxicity in SH-SY5Y cells by inducing oxidative stress, increasing DNA damage, and ultimately increasing apoptosis.Öğe Mechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells(Humana Press Inc, 2023) Yulak, Fatih; Filiz, Ahmet Kemal; Joha, Ziad; Ergul, MustafaThe PI3K pathway plays a crucial role in tumor cell proliferation across various cancers, including colon cancer, making it a promising treatment target. This study aims to investigate the antiproliferative activity of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor, on colon cancer and elucidate the underlying mechanisms. HT-29 colon cancer cells were treated with varying doses of ETP 45658 and its cytotoxic effect assessed using the XTT cell viability assay.ELISA was also used to measure TAS, TOS, Bax, BCL-2, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels. Flow cytometry was performed to investigate apoptosis, cell cycle, caspase 3/7 activity, and mitochondrial membrane potential. Additionally, following the administration of DAPI (4,6-diamidino-2-phenylindole) dye, the cells were visualized using an immunofluorescence microscope. It was observed that ETP-45658 exerted a dose-dependent and statistically significant antiproliferative effect on HT-29 colon cancer cells. Further investigations using the IC50 dose showed that ETP-45658 decreased TAS levels and increased TOS levels and revealed that it upregulated apoptotic proteins while downregulating anti-apoptotic proteins. Our findings also showed that it increased Annexin V binding, arrested the cell cycle at G0/G1 phase, induced caspase 3/7 activity, impaired mitochondrial membrane potential, and ultimately triggered apoptosis in HT-29 cells. ETP-45658 shows promise against colon cancer by inducing cell death, and oxidative stress, and arresting the cell cycle. Targeting the PI3K/AKT/mTOR pathway with ETP-45658 offers exciting potential for colon cancer treatment.Öğe Possible Interaction of Oxidative Stress, Inflammatory, and Nitric Oxide Pathways in the Anticonvulsant Effect of Vortioxetine on Pentylenetetrazole-Induced Seizures in Rats(Maik Nauka/Interperiodica/Springer, 2024) Taskiran, Ahmet Sevki; Filiz, Ahmet KemalAntidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures and underlying mechanisms. The aim here was to examine the impact and possible mechanisms of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioural testing was performed using passive avoidance and open-field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-alpha, IL-1 beta, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine pretreatment was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.Öğe Primer hipertansiyonlu bireylerde vasküler endotelyal growth faktör ve Tie-2 reseptör düzeylerinin belirlenmesi(Cumhuriyet Üniversitesi, 2013) Filiz, Ahmet Kemal; Özdemir, ErcanPrimer hipertansiyon etyopatogenezi ile ilgili olarak şimdiye kadar birçok faktörün etkili olabileceği ortaya konmuştur. Bu faktörlerden birisi de anormal anjiyogenezdir. Biz bu çalışmada, hipertansif bireylerde bir anjiyogenik faktör olan VEGF ile anjiyopoetin reseptörü olan Tie-2 reseptörlerinin düzeylerini ve hipertansiyonla ilişkili olabilecek bazı biyokimyasal parametreleri incelemeyi amaçladık. Çalışmamıza 90 birey primer hipertansiyonu olan 30 hasta (Hasta grubu) ve ailede hipertansiyon hikayesi olan sağlıklı 30 kişi (Kontrol 2 grubu) ile ailede hipertansiyon hikayesi olmayan sağlıklı 30 birey (Kontrol 1 grubu) olarak 3 gruba ayrıldı. Hastaların kan basınçları ölçüldü. Biyokimyasal parametrelerine bakıldı. VEGF ve Tie-2 düzeyleri ELISA yöntemiyle belirlendi. İstatistiksel yöntem olarak Kruskal Wallis ve Mann Whitney U testleri kullanıldı Hasta grupta Tie-2, VEGF, LDL ve Trigilerid düzeylerini yüksek, HDL düzeyini ise düşük olarak tespit ettik. (p<0,05). Hipertansiyon evresi ile Tie-2 arasında korelasyon varken (p<0,05), VEGF arasında korelasyon yoktu. (p>0,05) Sonuç olarak, elde ettiğimiz bulgular VEGF ve Tie-2 reseptörlerinin primer hipertansiyonla ilişkili olabileceğini göstermiştir. Ancak VEGF ve Tie-2 reseptörlerinin hipertansiyonlu hastalarda uzun dönemde kardiyovasküler hastalıklar açısından prognozu göstermedeki rolünü anlamak için daha ileri araştırmalara ihtiyaç vardır.Öğe Protective effects of lamotrigine and vitamin B12 on pentylenetetrazole-induced epileptogenesis in rats(Academic Press Inc Elsevier Science, 2021) Filiz, Ahmet Kemal; Gumus, Erkan; Karabulut, Sebahattin; Tastemur, Yasar; Taskiran, Ahmet SevkiEpileptogenesis is a process that includes molecular and cellular events that foster the establishment of hyperexcitable neuronal networks in the brain. Pentylenetetrazole (PTZ)-induced kindling model in rodents has added new information to the knowledge about the pathogenesis of epilepsy and potential targets of novel antiepileptic agents. Evidence from animal and human studies suggests that oxidative and inflammatory events may play important roles in the initiation and maintaining seizure activities. Vitamin B12 has beneficial effects on the nervous system and presents pleiotropic effects with antioxidant and anti-inflammatory aspects. In the present study, we aimed to test the hypothesis that vitamin B12 and their combination with lamotrigine prevents behavioral deficits, hippocampal damage, oxidation, and proinflammatory state during epileptogenesis. Male rats were subjected to PTZ-induced epileptogenesis and pretreated with vitamin B12 (50 mu g/kg) or Lamotrigine (LTG) (25 mg/kg) or B12 (50 mu g/kg) + LTG (25 mg/kg). Vitamin B12 and its combination with LTG suppressed epileptogenesis and improved the performance of rats in the passive avoidance test. In addition, Vitamin B12 and its combination with LTG decreased levels of total oxidative status (TOS), oxidative stress index (OSI), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and increased total antioxidant status (TAS) levels in the hippocampus and cerebral cortex. Furthermore, it reduced hippocampal neuronal damage. Current findings support the beneficial actions of vitamin B12 due to its antioxidative and anti-inflammatory properties during the course of disease. (C) 2021 Elsevier Inc. All rights reserved.Öğe Role of dopaminergic system in oxytocin analgesia: The missing part in a puzzle(Pharmacotherapy Group, 2020) Tastemur, Yasar; Taskiran, Ahmet Sevki; Altun, Ahmet; Filiz, Ahmet Kemal; Gulmez, Kader; Cimen, Kaan; Ozdemir, ErcanPurpose: To investigate the analgesic effects of oxytocin (OT) and elucidate the role of dopaminergic system in its mechanisms. Methods: In this study, 72 male (n=6 for each group) 230-250 gr Wistar Albino rats were used. Firstly, dose studies were performed with 100 mu g/kg, 200 mu g/kg and 400 mu g/kg to determine the optimal analgesic effect of oxytocin. Optimal dose was found at 200 mu g/kg, and then animals were divided into nine groups: Saline, D1 agonist (SKF 38393; 0.1 mg/kg), D1 antagonist (SCH-23390; 0.1 mg/kg), D1 agonist + oxytocin, D1 antagonist + oxytocin, D2 agonist (Cabergoline; 0,5 mg/kg), D2 antagonist (Sulpride; 10 mg/kg), D2 agonist + oxytocin and D2 antagonist + oxytocin. Serum physiologic saline was given to the saline group and other drugs were administered intraperitoneally at the indicated doses. Tail-flick and hot-plate tests were used to measure analgesic effects. Analgesic tests were measured in 30 min-intervals (at 30th, 60th, 90th, and 120th min) and recorded in seconds. To evaluate maximum antinociceptive effect (% MPE), the tail-flick and hot-plate latencies were converted to the antinociceptive effectiveness Results: The results show that D1 antagonist SCH-23390 (0.1 mg/kg) and D2 agonist cabergoline (0.5 mg/kg) created strong analgesia while the D1 agonist SKF 38393 (0.1 mg/kg) and D2 antagonist sulpiride (10 mg/kg) did not have any analgesic effect. However, only D2 antagonist sulpiride blocked the analgesic effect produced by OT Conclusion: OT may be one of the primary agents participating in spinal analgesia, and the dopaminergic system is one of the central mechanisms of action for this important molecule. The dopaminergic system may also be one of the targets for 'descending' analgesic system.Öğe The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy(Academic Press Inc Elsevier Science, 2021) Filiz, Ahmet Kemal; Gumus, Erkan; Karabulut, Sebahattin; Tastemur, Yasar; Taskiran, Ahmet SevkiPurpose: To assess the possible contribution of factors in additional to intrauterine anti-seizure medication (ASM) exposure in the occurrence of fetal malformation in women with ASM-treated epilepsy. Results: Logistic regression analysis showed that maternal age over 31 years, family histories of fetal malformation, and conception after assisted fertility treatment, and also dosage of valproate, carbamazepine, and topiramate, made statistically significant (P < 0.05) contributions to the fetal malformation rate in 2223 pregnancies in Australian women with epilepsy. The malformation rates were lower in pregnancies where the non-ASM-associated contributory factors were not present: statistically significantly so for all ASM-exposed pregnancies, and those pregnancies exposed to the more potent teratogenic drugs. Conclusion: It is important to consider the possible roles of identified, and also possible non-identified, non-ASM factors in relation to the occurrence of fetal malformations in the pregnancies of women with ASM-treated epilepsy. (C) 2021 Elsevier Inc. All rights reserved.Öğe The effect of penicillin-induced epileptiform activity on proinflammatory cytokines levels in the rat brain(2021) Filiz, Ahmet Kemal; Karabulut, SebahattinEmerging evidence indicates a pathogenic role of protracted neuroinflammation in the various neurodegenerative diseases, including epilepsy. Neuroinflammation may contribute to neuronal hyperexcitability underlying seizure formation. The current research aims to examine the changes in the levels of proinflammatory cytokines such as interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) in the penicillin epilepsy model. In the present study, 12 male Wistar albino rats were randomly divided into two groups as sham and penicillin epilepsy model. Seizures were induced with the intracortical (i.c.) single microinjection 500 IU of penicillin-G into neocortex. Rats were decapitated after observing the cortical epileptic activity and brains were removed by craniotomy. Proinflammatory cytokines (TNF-? and IL-1?) were measured by using ELISA methods in the cortical and hippocampal brain regions. Penicillin significantly up-regulated the expression of IL 1? and TNF-? in the rat cortex, but did not affect the hippocampal cytokines levels. This study is indicative of the neuroinflammatory potential of cortical penicillin administration.Öğe The Role of Nitric Oxide Pathway in the Anti-Epileptogenic Effect of Valproic Acid in the Pentylenetetrazole-Kindling Model in Rats(Maik Nauka/Interperiodica/Springer, 2023) Sahin, Bilal; Filiz, Ahmet Kemal; Joha, ZiadThough valproic acid (VPA) is used to treat seizures, more investigations have been needed to understand the effect of VPA on the nitric oxide pathway in epilepsy. Our investigation aimed to study the effect of VPA on cortical and hippocampal NOS isomers in epileptogenesis processes in the PTZ kindling model of epilepsy in the rat to reveal its mechanisms of action. Twenty-four male Wistar albino rats were used in this study. The animals were divided into four groups control, PTZ without VPA, and PTZ with VPA at two doses (100 and 200 mg/kg) Rats were kindled by injections of PTZ (35 mg/kg) with drugs or vehicle 30 minutes before, once every other day for 12 times and their behavior was observed. After completing the epileptic model process, nitric oxide pathway markers (eNOS, nNOS, iNOS, and NO) in the cortex and hippocampus were assessed by using ELISA methods. VPA suppressed seizure stages and decreased nNOS, iNOS, and NO levels while increasing eNOS levels in the hippocampus and cerebral cortex. The effect of VPA on nitric oxide pathway was found to contribute to its anti-epileptic activity.
