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

Abstract

SUMMARYObjective: 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 ÖZET 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) 653 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....

Pathophysiological Cascade of Events Leading to Epilepsy: Role of Inflammation

“…Studies in rats have also closely linked HMGB1 to reduced cognitive abilities related to neuroinflammation, TBI, and epilepsy [28,29]…”

“…Two COX isozymes are known: COX-1, which is constitutively produced in almost all body tissues, and COX-2, predominantly produced in brain tissues after various insults, thus contributing to the brain inflammation involved in the long-term consequences of such insults [28]. Experimental studies conducted on rat models have shown a significant protective role of selective COX-2inhibitors against epilepsy and neuronal damage despite the unclear role of COX-2 on the pathogenesis of epilepsy [29]. Because of this neuroprotection role, celecoxib, a selective COX-2-inhibitor non-steroidal anti-inflammatory medication, is currently prescribed as an antiepileptogenesis disease-modification drug following brain insults like status epilepticus, cerebral ischemic injuries or head trauma.…”

“…COX-2 is involved in the activation of the astrocytes, brain inflammatory reaction, death of neurons, enhanced neuronal excitability, cellular proliferation, and growth and spread of many tumors [30,31,32]. Inhibition of COX by nonsteroidal anti-inflammatory drug drugs decreases neurogenesis and causes a dentate gyrus following acute global ischemia [29,33] Fig. 4.…”