Acute Administration of High Dose Trimetazidine Inhibits Pentylenetetrazol-Induced Seizures in Rats

Abstract

SUMMARYObjective: Resistant epilepsy is widely seen in clinical settings manipulate the researchers to pursuit novel anti-epileptic treatments. Although trimetazidine (TMZ) is commonly used in the treatment of angina and ischemic diseases, it is considered that the drug may be beneficial in the treatment of epileptic seizures and convulsions. We aimed to evaluate electrophysiologically the protective effects of high dose acute TMZ on epileptic seizures and convulsions in a rat model of epilepsy induced by pentilentetrazol (PTZ). Method: Forty-eight male Sprague-Dawley rats were used for the EEG evaluation (Group-A; n=24) and behavioral assessment (Group-B; n=24). Grup-A1 and Grup-B1 were determined as control group and given no medication. 35 mg/kg (Group-A2, -A3 and -A4) and 70 mg/kg (Group-B2, -B3 and -B4) of PTZ were administered intraperitoneally (ip.) so as to generate seizures and convulsions. Group-A2 and Group-B2 were treated with saline. 40 mg/kg (Grup-A3 and Grup-B3) and 80 mg/kg of TMZ (Group-A4 and Group-B4) were administered to the treatment groups by ip. Brain malondialdehyde (MDA) levels, spike-percentage values, Racine's Convulsion Scale (RCS) scores and "first myoclonic jerk (FMJ)" latencies of each rat were determined. Results: Brain MDA levels, spike-percentage values, RCS scores, and FMJ latencies of Group-A2 and Group-B2 were significantly increased compared to those of the control's (Grup-A1 and Grup-B1) (P<0.05 for all comparisons). However, in TMZ treated groups (Group-A3 and -A4; Group-B3 and -B4) the elevated values of these parameters were found to be significantly decreased (P<0.05 for all comparisons). Conclusions:This study has demonstrated that the high dose acute TMZ administration may prevent PTZ-induced seizures and convulsions in rats. Furthermore, it can be also said that TMZ has a neuroprotective effects on oxidative stress associated with PTZ. Therefore, it may be considered for use with therapeutic purposes of TMZ in resistant epilepsy patients in the future. Keywords: Electroencephalography (EEG), Epilepsy, Malondialdehyde, Pentylenetetrazol, Rat, Trimetazidine.ÖZET Amaç: İlaca-dirençli epilepsi, klinikte yaygın olarak görülen ve araştırmacıları yeni anti-epileptik tedavilerin saptanması için harekete geçiren bir durumdur. Trimetazidin (TMZ) anjina ve iskemik hastalıkların tedavisinde yaygın olarak kullanılmasına rağmen, epileptik nöbetler ve konvülsiyonların tedavisinde de yararlı olabileceği düşünülmektedir. Bu çalışmada, pentilentetrazol (PTZ) ile indüklenen bir sıçan epilepsi modelinde yüksek doz akut TMZ'nin epileptik nöbetler ve konvülsiyonlar üzerine koruyucu etkilerini elektrofizyolojik parametreler açısından değerlendirmeyi amaçladık. 381Yöntem: 48 adet erkek Sprague-Dawley cinsi sıçan EEG (Group-A; n=24) ve davranış analizlerinde (Group-B; n=24) kullanıldı. Grup-A1 ve Grup-B1 kontrol grubu olarak belirlendi ve ilaç verilmedi. 35 mg/kg (Group-A2, -A3 ve -A4) ve 70 mg/kg PTZ (Group-B2, -B3 ve -B4), nöbet ve konvülsiyon oluşturmak amacıyla, intraperitoneal olarak (i...

Oxidative stress in epilepsy

“…В исследованиях S. Gurgul и соавт. [20] также проводилось изучение уровня свободных радикалов (гидроксильных и нитроксильных) в ткани мозга крыс линии Вистар после однократного эпилептического приступа. Значительное увеличение уровня свободных радикалов определялось через 60 мин после приступа, но не сразу после него (1 мин и 15 мин).…”