Investigation of the Effect of Diazepam on Nitric Oxide Synthase and Brain-Derived Neurotrophic Factor in Pentylenetetrazole-Induced Acute Seizure Model

Year 2022, , 52 - 57, 29.06.2022

Bilal Şahin , Handan Güneş

https://doi.org/10.46810/tdfd.1002192

Abstract

The aim of this study was to investigate the effect of diazepam on nitric oxide synthase (NOS) and brain-derived neurotrophic factor (BDNF) in the anti-convulsant activity of diazepam on pentylenetetrazole (PTZ) induced seizures in rats. 24 male Wistar Albino rats were used in the study. Rats were divided into 4 groups as control group, saline (1 mL kg-1) +PTZ, diazepam (0.5 mg kg-1) +PTZ and diazepam (2 mg kg-1) +PTZ group (n=6). For biochemical studies, 24 hours after PTZ application, brain tissues of all rats were removed and cortex and hippocampus regions were isolated NOS and BDNF levels in the cortex and hippocampus were measured using ELISA kits. Diazepam significantly decreased the seizure stage and prolonged the first myoclonic jerk (IMJ) time compared to the saline group (p<0.001). Saline+PTZ significantly decreased NOS levels in the hippocampus when compared to the control group (p<0.05). However, the diazepam+PTZ groups significantly increased the hippocampal NOS level compared to the saline+PTZ group (p<0.001). In addition, the saline + PTZ group increased the BDNF level in the cortex and hippocampus compared to the control (p<0.05), while the BDNF level was lower in the diazepam+PTZ group compared to the saline+PTZ group (p<0.001). Diazepam increased NOS levels in the hippocampus and decreased BDNF levels in the cortex and hippocampus. In conclusion, the regulatory effect of diazepam on NOS and BDNF may be related to its anti-convulsant mechanisms.

Keywords

Seizure, Pentylentetrazole Diazepam, Nitric Oxide Syntase, Brain Derived Neurotrophic Factor

Pentilentetrazol ile Oluşturulan Akut Nöbet Modelinde Diazepamın Nitrik Oksit Sentaz ve Beyin Kaynaklı Nörotrofik Faktör Üzerine Etkisinin Araştırılması

Abstract

Bu çalışmanın amacı, sıçanlarda pentilentetrazol (PTZ) ile oluşturulan nöbetlerde diazepamın antikonvulzif etkinliğinde nitrik oksit sentaz (NOS) ve beyin kaynaklı nörotrofik faktör (BDNF) üzerine etkisini araştırmaktır. Çalışmada 24 adet erkek Wistar Albino sıçan kullanılmıştır. Sıçanlar kontrol grubu, salin (1 mL kg-1) + PTZ, diazepam (0,5 mg kg-1) + PTZ ve diazepam (2 mg kg-1)+PTZ grubu olarak 4 gruba ayrılmıştır (n=6). İntraperitoneal ilaç uygulamalarından 24 saat sonra biyokimyasal incelemeler için tüm sıçanların beyin dokuları çıkarılıp, korteks ve hipokampüs bölgeleri ayrılmıştır. Korteks ve hipokampüsteki NOS ve BDNF düzeyleri enzim bağlı immünosorbent analizi (ELISA) kitleri kullanılarak ölçülmüştür. Diazepam, salin+PTZ uygulanan grubuna göre istatistiksel açıdan anlamlı bir şekilde nöbet evresini azalttı ve ilk miyoklonik jerk (İMJ) süresini uzattı (p<0.001). Salin+PTZ, kontrol grubuna kıyasla hipokampüste NOS seviyelerini anlamlı olarak azalttı (p<0.05). Bununla birlikte diazepam+PTZ grupları, salin+PTZ grubuyla karşılaştırıldığında hipokampal NOS seviyesini anlamlı olarak artırdı (p<0.001). Ayrıca,salin+PTZ grubu kontrolle karşılaştırıldığında korteks ve hipokampüste BDNF seviyesini artırırken (p<0.05), diazepam+PTZ uygulanan gruplarda BDNF seviyesi salin+PTZ grubuna kıyasla düşüktü (p<0.001). Diazepam hipokampüste NOS seviyesini artırmış, korteks ve hipokampüste ise BDNF seviyelerini düşürmüştür. Sonuç olarak, diazepamın NOS ve BDNF üzerine regülatif etkisi antikonvulsif etkisiyle ilişkili olabilir.

Keywords

Nöbet, Pentilentetrazol (PTZ), Diazepam, Nitrik Oksit Sentaz (NOS), Beyin Kaynaklı Nörotrofik Faktör (BDNF)

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