Interaction between carbenoxolone and valproic acid on pentylenetetrazole kindling model of epilepsy

Sefil F., Arik A. E., Acar M. D., BOSTANCI M. Ö., Bagirici F., Kozan R.

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol.8, no.7, pp.10508-10514, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 8 Issue: 7
  • Publication Date: 2015
  • Journal Name: INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.10508-10514
  • Keywords: Gap junction, carbenoxolone, valproic acid, kindling model, epilepsy, GAP-JUNCTION BLOCKERS, ANTICONVULSANT EFFICACY, ANTIEPILEPTIC DRUGS, SEIZURE ACTIVITY, IN-VIVO, RATS, HIPPOCAMPUS, MICE, QUININE, FUTURE
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

Gap junctions play an important role in the synchronized neuronal discharges. The main reason of the epileptic seizures is disruption of this synchronization. Therefore, the aim of the present study is to explore the combination valproic acid with carbenoxolone in pentylenetetrazole-kindled rats. In the first set of experiments, pentylenetetrazole (35 mg/kg intraperitoneally was administered to the rats to produce the kindling and then permanent screw electrodes to record electroencephalographic signals. The kindled rats were divided into six groups. While electroencephalographic recordings received from animals, behavioral evaluation was done by an observer. The data analysis was performed using T test and Mann-Whitney U tests. The dose of 40 mg/kg carbenoxolone was the most effective in carbenoxolone treatment groups. It prevented generalized seizures by 50%, reduced seizure stage, seizure duration and spike frequency. There was no significant difference between carbenoxolone-valproic acid combination and valproic acid on any seizure parameters. The current study is the first study which shows the interaction of carbenoxolone with valproic acid in pentylenetetrazole kindling model. As a result, carbenoxolone-valproic acid combination was not more effective than the standalone use of these drugs.