Sule AYDIN, Çiğdem TOPRAK, Çiğdem ÇENGELLİ ÜNEL, Bilgin KAYGISIZ, Kevser EROL

Farelerde Pentilenetetrazol ile İndüklenen Epilepsi Modelinde Agmatinin Etkilerinin ve Nitrik Oksitin Katkısının Araştırılması

Amaç: Agmatin, endojen katyonik bir amindir ve α2-adrenoseptörler, imidazolin bağlanma yerleri, NMDA reseptörleri ve nitrik oksit (NO) sentaz inhibisyonu aracılığıyla çeşitli nöroterapötik etkileri bildirilmiştir. NO' nun ise merkezi sinir sisteminde nöromodülatör ve nörotransmiter olarak görev yaptığı ve konvülziyon modellerinde prokonvülsan/ antikonvülsan aktiviteye sahip olduğu bildirilmiştir. Biz de agmatin, sodyum valproat, gabapentin ve fenitoinin antikonvülsan aktivitelerini karşılaştırmayı ve ilaçların etkilerinde NO' nun rolünü araştırmayı amaçladık. Gereç ve yöntemler: Epilepsi nöbetleri, Swiss-albino farelerde tek doz pentilentetrazol (PTZ) (60 mg/kg) enjeksiyonu ile indüklendi. Farelerin miyoklonik kasılma (MJ) ve jeneralize tonik-klonik nöbetleri (GTCS) kaydedildi. Agmatin (10 mg/kg), sodyum valproat (150 mg/kg), gabapentin (20 mg kg) ve fenitoin (20 mg / kg) tek başına veya nitrik oksit prekürsörü N(G)-Nitro-L-arginin-metil-ester (L-NAME, 5 mg/kg) ve spesifik olmayan NO sentaz inhibitörü NO, L-arginin (L-Arg, 60 mg/kg) ile kombinasyon halinde ve intraperitoneal olarak enjekte edildi. Bulgular: Agmatin ve sodyum valproat % GTCS' yi önemli ölçüde engelliyorken, fenitoin ve gabapentin engellemedi. L-Arg, % MJ üzerinde agmatinin aktivitesini önemli ölçüde azalttı. Hem L-Arg hem de L-NAME, fenitoinin % MJ ve % GTCS üzerine olan aktivitesini etkilemedi. L-Arg, gabapentinin % MJ ve % GTCS üzerine olan aktivitesini değiştirmedi. L-NAME, gabapentinin % MJ ve % GTCS üzerine olan aktivitesini önemli ölçüde artırdı. Sonuç Bu çalışma, NO' nun agmatin ve gabapentinin antikonvülsan aktivitesi üzerinde bir rolü olabileceğini, ancak sodyum valproat ve fenitoinin rolü olmadığını önermektedir.

Anahtar Kelimeler:

agmatin, sodyum valproat, gabapentin, fenitoin, nitric oksit

The Investigation of the Effects of Agmatine in Pentylenetetrazole-induced Epilepsy Model in Mice and the Contribution of Nitric Oxide

Objective: Agmatine is an endogenous cationic amin and have been reported several neurotherapeutic effects through α2-adrenoceptors, imidazoline binding sites, inhibition of NMDA receptors and nitric oxide (NO) synthase. NO was reported to act as a neuromodulator and neurotransmitter in central nervous system and has proconvulsant/anticonvulsant activities in convulsion models. We aimed to compare the anticonvulsant activities of agmatine, sodium valproate, gabapentin and phenytoin, and to investigate the role of NO in effects of drugs. Material and Methods: Epilepsy seizures were induced in swiss-albino mice by single dose injection of penthylenetetrazole (PTZ) (60 mg/kg). Myoclonic-jerk (MJ) and generalized tonic-clonic seizures (GTCS) of mice were recorded. Agmatine (10 mg/kg), sodium valproate (150 mg/kg), gabapentin (20 mg/kg) and phenytoin (20 mg/kg) alone or in combinations with N(G)-Nitro-L-arginine-methyl-ester (L-NAME, 5 mg/kg), the precursor of NO, L-arginine (L-Arg, 60 mg/kg) and non-specific NO synthase inhibitor, were injected intraperitoneally. Results: While agmatine and sodium valproate significantly prevented GTCS%, phenytoin and gabapentin did not prevent. L-Arg significantly reduced activity of agmatine on MJ%. Both L-Arg and L-NAME did not affect activity of phenytoin on MJ% and GTCS%. L-Arg did not change the activity of gabapentin on MJ% and GTCS%. L-NAME significantly increased activity of gabapentin on MJ% and GTCS%. Conclusion: This study suggested that NO may have a role on anticonvulsant activity of agmatine and gabapentin but not those of sodium valproate and phenytoin.

Keywords:

agmatine, sodium valproate, gabapentin, phenytoin, nitric oxide,

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