Metforminin Tek Başına veya Valproik asit ile Beraber Farelerde Pentilentetrazol ile İndüklenen Nöbetler Üzerine Koruyucu Etkisi

Year 2022, Volume: 17 Issue: 3, 15 - 21, 02.11.2022

Erkan Gümüş Mustafa Ergül Kader Gülmez Mustafa Ulu Recep Akkaya Ercan Özdemir Ahmet Şevki Taşkıran

https://doi.org/10.17517/ksutfd.914271

Abstract

Özet

Amaç: Bu çalışmanın amacı, metforminin pentilentetrazol (PTZ) ile indüklenen nöbet davranışı üzerindeki etkilerini ve nöronal hasar üzerindeki nöroprotektif etkisini araştırmaktır.
Gereç ve Yöntemler: 35-38 gram ağırlığındaki otuz beş (35) erkek BALB-c Albino fare rastgele beş gruba ayrıldı: Kontrol grubu (1), Salin+PTZ grubu (2), Valproik Asit (VPA 200 mg/kg i.p.)+PTZ grubu (3), Metformin (200 mg/kg i.p.)+PTZ grubu (4) ve VPA+Metformin+PTZ grubu (5). PTZ (60 mg/kg, intraperitoneal-
i.p.), nöbetleri indüklemek için ilaç enjeksiyonundan 30 dakika sonra enjekte edildi ve nöbet aşamaları ve davranışsal skorlama değerlendirildi. İşlem tamamlandıktan sonra beyin dokuları çıkarıldı ve biyokimyasal ve histopatolojik prosedürlerle analiz edildi. Hipokampal Cornu Ammonis (CA)1, CA2, CA3
ve DG (dentat girus) bölgeleri histopatolojik olarak değerlendirildi ve oksidatif stres belirteçleri (toplam antioksidan durum (TAS), toplam oksidan durum (TOS)) ölçüldü.
Bulgular: Salin+PTZ grubuyla karşılaştırıldığında, Metformin tek başına ilk miyoklonik jerk (FMJ) başlangıç süresini etkilemedi, ancak VPA ve metformin kombinasyonun FMJ başlangıç süresini anlamlı derecede artırdığı izlendi (p<0.05). Ek olarak, VPA ile beraber ve/veya VPA olmadan metformin tedavisi beyin
oksidatif stresini önemli ölçüde azalttı (p<0.05). Ayrıca, histopatolojik değerlendirme ile metformin uygulamasının ve VPA+metformin kombinasyonunun hipokampal CA1, CA2, CA3 ve DG alanlarındaki dark nöron oluşumunu azalttığı saptandı (p<0.05).
Sonuç: Metforminin, epileptik nöbetleri ve beyin oksidatif stresini azalttığı ve PTZ ile indüklenen nöbet sonrası nöral hasarı önlediği tespit edilmiştir.

Keywords

Metformin, Epilepsi, Pentylenetetrazole, Nöronal hasar

Protective Effect of Metformin Alone or in Combination with Valproic acid on Pentylenetetrazole-Induced Seizures in Mice

Abstract

Abstract

Objective: The aim of this study was to investigate the effects of metformin on pentylenetetrazole (PTZ)-induced seizures and the neuroprotective effect of metformin on neuronal damage after pentylenetetrazole administration.
Material and Methods: Thirty-five (35) Male BALB-c Albino mice weighing 35-38 g were divided randomly into five groups: Control group (1), Saline+PTZ group (2), Valproic Acid (VPA, 200 mg/kg intraperitoneal-i.p.)+PTZ group (3), Metformin (200 mg/kg i.p.)+PTZ group (4), and VPA+Metformin+PTZ
group (5). The PTZ (60 mg/kg, i.p.) was injected 30 min after drugs injection to induce seizures and seizure stages and behavioral scoring were evaluated. After completing procedure, brain tissues were removed and analyzed with biochemical and histopathological procedures. The hippocampal Cornu Ammonis (CA) 1, CA2, CA3 and DG (dentate gyrus) regions were histopathologically evaluated and oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS)) were measured.
Results: Compare to Saline+PTZ group, metformin administration alone did not affect the onset time of the first myoclonic jerk (FMJ), but combination of VPA and metformin significantly increased FMJ onset time (p<0.05). Additionally, the treatment of metformin with or without VPA reduced the brain oxidative
stress (p<0.05). Furthermore, histopathological assessment demonstrated that metformin administration and the combination of VPA and metformin decreased dark neuron formation in the hippocampal CA1, CA2, CA3, and DG areas (p<0.05).
Conclusion: Metformin was found to be significantly effective in reducing epileptic seizures, brain oxidative stress, and preventing neural damage after PTZ-induced seizure

Keywords

Metformin, Epilepsy, Pentylenetetrazole, Neuronal damage

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