Phenytoin Attenuates Seizure Severity and Hippocampal Derangement than Levetiracetam or Phenytoin-Levetiracetam Adjunctive Treatment in Electrically-Convulsed Mice

This study evaluated the anticonvulsant and neuroprotective efficacy of individual or adjuvant treatment of two different antiepileptic-drugs (AEDs) phenytoin (PHT) and levetiracetam (LEV) against maximal electric shock in mice model. Twenty-five male Albino mice, randomized into five groups (n=5) received treatment as follows: groups 1 and 2 received intraperitoneal (i.p) administration of normal saline (0.1 ml), while groups 3-5 received a therapeutic dose of PHT (50 mg/kg BW) or LEV (50 mg/kg/day BW), or combination of PHT (25 mg/kg) and LEV (25 mg/kg) at sub-therapeutic doses. Thirty minutes later, the mice in groups 2-5 were challenged with maximal electroshock, while various indices of convulsion were determined, while the histomorphological profile of the hippocampus investigated. Data were analyzed using descriptive and inferential statistics with the help of graph pad prism software. The results were presented as mean ± SEM in the graph or table. The level of significance was taken at p<0.05. There was a decrease (p = 0.0001) in the duration of tonic flexion, tonic limb extension, clonic convulsion, stupor, and righting reflex in all the drug-treated groups compared with positive control. Also, the duration of clonic convulsion significantly decreased in the PHT (p = 0.0003) and PHT + LEV treated mice compared with LEV treated. There was significant (p = 0.0001) damage in the neuronal hippocampal tissue of the untreated mice. Funding Information: The authors declared that this research was self-sponsored. Declaration of Interests: The authors declared that this research was conducted in the absence of any commercial or financial relationships that could interpret as potential conflict of interest. Ethics Approval Statement: The experimental protocol was approved by the Health Research Ethics Committee, Institute of Public Health, Obafemi Awolowo University, Ile –Ife which also comply with the ARRIVE guidelines and should be carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments.