Investigation of the Effect of Folic Acid on Ethosuximide in Pentylenetetrazole-Induced Acute Seizures in Mice

Abstract

Purpose: Epilepsy is one of the most prevalent neurological diseases today. Despite various treatments, there is still no complete seizure control. Studies have shown the positive effects of folic acid (FA) and its derivatives on seizures. The objective of this study is to investigate Caspase-3 and TOS activity in brain tissues as well as the effect of folic acid on ethosuximide (ETX) in mice with pentylenetetrazol-induced seizures.

Materials and Methods: In this study, 30 mice of BALB/c species were divided randomly into 5 groups: Control; pen-tylenetetrazol (PTZ); PTZ-induced seizure group; FA in which 3 mg/kg FA and PTZ were administered for 7 days; ETX in which 50 mg/kg ETX and PTZ were administered for 7 days; FA+ ETX in which 3 mg/kg FA and 50 mg/kg ETX and PTZ were administered for 7 days. The brain tissues of all mice were dissected, then the cortex and hippocampus were separated 24 hours after PTZ application.

Results: FA, ETX and FA+ETX groups significantly decreased the seizure stage compared to the PTZ group, and similarly prolonged the first myoclonic jerk times, but the FA and FA+ETX groups were found to decrease the onset of generalizedtonic–clonic seizures (p<0.05). However, the FA and FA+ETX groups decreased the hippocampal TOS levels. (p<0.05). Similarly, hippocampal caspase-3 levels were lower in the FA group (p<0.05).

Conclusion: FA can be a useful therapeutic agent for the treatment of epilepsy with its antioxidant and antiapoptotic properties. The synergistic effect of FA with ETX can promote its protective effect against neuronal damage

Keywords

• ethosuximide
• folic acid
• pentylenetetrazole (PTZ)

Folik Asitin Etosüksimid Üzerine Etkisinin Farelerde Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde İncelenmesi

Abstract

Amaç: Epilepsi, günümüzde en sık görülen nörolojik hastalıklardan biridir. Çeşitli tedavilere rağmen hala tam olarak nöbet kontrolü sağlanamamaktadır. Yapılan çalışmalar folik asit (FA) ve türevlerinin nöbetler üzerine olumlu etkiler ortaya koymuştur. Bu çalışmanın amacı, farelerde pentilentetrazol ile oluşturulan nöbet-lerde folik asitin etosüksimid üzerine etkisinin yanında beyin dokularında kaspaz-3 ve TOS aktivitesini araştırmaktır.

Araçlar ve Yöntem: Çalışmada BALB/c türü 30 fare rastgele 5 gruba ayrıldı: Kontrol, pentilentetrazol (PTZ); PTZ ile nöbet indüklenen grup, FA; 7 gün boyunca 3 mg/kg verilen ve PTZ uygulanan grup, etosüksimid; 7 gün boyunca 50 mg/kg verilen ve PTZ uygulanan grup, FA+ etosüksimid; 7 gün boyunca 3 mg/kg FA ve 50 mg/kg etosüksimid verilen ve PTZ uygulanan grup. PTZ uygulamasından 24 saat sonra tüm farelerin beyin dokuları çıkarıldı, korteks ve hipokampus ayrıldı.

Bulgular: Folik asit, etosüksimid ve FA+ etosüksimid grupları PTZ grubuna göre nöbet evresini anlamlı olarak azalttı, benzer şekilde first miyoklonik jerk sürelerini uzattı ancak jeneralize tonik-klonik nöbete giriş zamanını FA ve FA+ etosüksimid gruplarının azalttığı bulundu (p<0.05). Bununla birlikte FA ve FA+ etosüksimid grupları, hipokampal TOS seviyesini azalttı. (p<0.05). Benzer şekilde, hipokampal kaspaz-3 seviyesi FA uygulanan grupta daha düşük bulundu (p<0.05).

Sonuç: FA antioksidatif ve antiapoptotik özellikleriyle epilepsi tedavisi için faydalı bir terapotik ajan olabilir. Folik asit, etosüksimid ile sinerjik etkisi nöronal hasara karşı koruyucu etkisini güçlendirebilir.

Keywords

• etosüksimid
• folik asit
• pentilentetrazol (PTZ)

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