Effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole-induced epileptic seizures in rats

Erkan Gumus; Ahmet Sevki Taskıran; Hacer Aybike Toptas; Özge Güney; Rukiye Kutlu; Handan Gunes; Ercan Ozdemir; Gokhan Arslan

doi:10.7197/223.v39i32356.369027

EN TR

Effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole-induced epileptic seizures in rats

Abstract

Objective: Epilepsy is a short-term paroxysmal disturbances of brain functions observed between sudden, abnormal and hypersynchronization discharges and seizures of a group of neurons in the central nervous system. The nonsteroidal anti-inflammatory tenoxicam is chemical agent that selectively inhibits type 2 cyclooxygenase (COX2), which converts arachidonic acid to prostaglandins (PGs). The aim of this study was to investigate the effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole on epileptic seizures.
Method: Eighteen Wistar Albino male rats (220±20 g) were divided into three groups: control (n=6), 10 mg/kg/day tenoxicam (n=6) and, 20 mg/kg/day tenoxicam (n=6). Tenoxicam was administered intramuscularly for ten days. On the tenth day, pentylenetetrazol (PTZ) was injected intraperitoneally at 70 mg/kg after 45 minutes of drug administration and the animals were observed for 30 min. Stages were determined according to the Racine seizure scale (RC) and the first myoclonic jerk time (FMJ) was recorded in seconds. After completing procedure, whole brain tissues were removed and stained with toluidine blue stain. The number of dark neurons with chromatin aggregation in hypocampal CA1 and dentate gyrus (DG) was determined as percentage.
Results: Epileptic behavior were evaluated according to the RC, 10 mg/kg of tenoxicam significantly reduced the seizure stage compared to the control (p<0,05). In addition, 10 mg/kg tenoxicam significantly increased the FMJ compared to the control (p<0,05). According to the histopathological findings, neuronal damage was increased in CA1 region of 20 mg/kg of tenoxicam group compared to control, whereas neuronal damage was reduced significantly in the dentate gyrus of 10 mg/kg and 20 mg/kg of tenoxicam groups (p<0,05).

Conclusions: This study shows that dose-dependent administration of tenoxicam might have a potential to reduce epileptic seizures and post-seizure neuron damage.

Keywords

Epilepsy,cyclooxygenase-2 inhibitor,tenoxicam,pentylenetetrazole

Siklooksijenaz-2 inhibitörü tenoksikam'ın pentilentetrazol ile oluşturulan epileptik nöbetler üzerine etkisi

Öz

Amaç: Epilepsi merkezi sinir sisteminde bir grup nöronun ani, anormal ve hipersenkronize deşarjları ile nöbetler halinde gözlenen beyin fonksiyonlarının kısa süreli paroksimal rahatsızlığı olarak tanımlanır. Nonsteroid anti inflamatuarlardan olan tenoksikam araşidonik asidi prostaglandinlere dönüştüren tip 2 siklooksijenaz (COX2) enzimini selektif olarak inhibe eden kimyasal bir ajandır. Bu çalışmanın amacı siklooksijenaz-2 inhibitörü tenoksikam'ın pentilentetrazol ile oluşturulan epileptik nöbetlere üzerine etkisini araştırmaktır.

Yöntem: Çalışmamızda 18 tane 220-240 gr Wistar Albino erkek sıçan kullanılmıştır. Hayvanlar kontrol (n=6), 10 mg/kg/gün tenoksikam (n=6) ve 20 mg/kg/gün tenoksikam (n=6) olmak üzere üç gruba ayrıldı. On gün süre ile kontrol grubuna çözücü ve diğer iki gruba belirtilen dozlarda tenoksikam intramusküler olarak uygulandı. Onuncu gün ilaç uygulamalarından 45 dk sonra pentilentetrazol (PTZ) 70 mg/kg intraperitoneal olarak enjekte edildi. Hayvanlar 30 dk boyunca gözlemlendi. Racine nöbet skalasına göre evreleri belirlendi ve ilk miyoklonik jerk zamanı (FMJ) saniye olarak kaydedildi. İşlem bitiminden sonra hayvanların beyin dokuları alındı. Beyin dokuları rutin histolojik takip sonrası toluidin blue boyası ile boyanandı. Hipokampüste CA1 ve dentat girus bölgelerinde nöronal hasarı gösteren ‘Dark nöron’ sayıları yüzde olarak belirlendi.

Bulgular: Epileptik davranış sonuçları Racine nöbet skalasına (RC) göre değerlendirildiğinde, 10 mg/kg tenoksikam kontrole göre nöbet evresini anlamlı olarak azalttı (p<0,05). Ayrıca 10 mg/kg tenoksikam kontrole göre ilk miyoklonik jerk zamanını anlamlı olarak arttırdı (p<0,05). Histopatolojik olarak gruplar değerlendirildiğinde, CA1 bölgesinde 20 mg/kg tenoksikam kontrole göre nöronal hasarı arttıdığı, buna karsışık dentat girus bölgelesinde 10 mg/kg ve 20 mg/kg tenoksikam nöronal hasarı anlamlı olarak azalttı (p<0,05).

Sonuç: Bu çalışma tenoksikam uygulamasının epileptik nöbetleri ve nöbet sonrası nöron hasarını doz bağımlı olarak azaltabileceğini göstermektedir.

Anahtar Kelimeler

Epilepsi,Siklooksijenaz -2 inhibitörü,tenoksikam,pentilentetrazol

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Details

Primary Language

English

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Erkan Gumus

Ahmet Sevki Taskıran

Hacer Aybike Toptas

Özge Güney

Rukiye Kutlu

Handan Gunes

Ercan Ozdemir

Gokhan Arslan

Publication Date

December 18, 2017

Submission Date

July 17, 2017

Acceptance Date

October 24, 2017

Published in Issue

Year 2017 Volume: 39 Number: 4

DOI

https://doi.org/10.7197/223.v39i32356.369027

IZ

https://izlik.org/JA69GH93JF

Cite

RIS / Bibtex

AMA

1.Gumus E, Taskıran AS, Toptas HA, et al. Effect of the cyclooxygenase-2 inhibitor tenoxicam on pentylenetetrazole-induced epileptic seizures in rats. CMJ. 2017;39(4):652-658. doi:10.7197/223.v39i32356.369027

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