Abstract
Background and purposeStudies in the animal models of epilepsy have suggested the anti-seizure effects of neuroactive steroids and its derivatives in kainic acid and pilocarpine induced limbic seizures and status epilepticus in mice, but no such studies have been reported in the published literature on the role of allopregnanolone in chemical kindling model and its interaction with sodium valproate. The purpose of this study was to evaluate the interaction between sodium valproate and allopregnanolone in pentylenetetrazole induced kindling model in rats. MethodsIn a PTZ kindled Wistar rat model, sodium valproate and allopregnanolone were administered 30min before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal anti-oxidant parameters and hippocampal DNA fragmentation studies. ResultsIn this study, the combination of low dose of allopregnanolone with low dose of sodium valproate showed a similar beneficial effect to that of a higher dose of sodium valproate in significantly reducing the number of kindled animals (0/8) as compare to PTZ control group (5/8) as well as the seizure scores and the histopathological scores. The combination significantly reduces oxidative stress by significantly decreasing the MDA levels, and increasing the SOD levels and GSH levels in the hippocampus of rats as compared to PTZ control group. So all these data suggest the antiepileptic effect of the combination and confers the synergistic interaction between the allopregnanolone and sodium valproate. ConclusionsIt can be concluded that by choosing this combination the dose of sodium valproate can be reduced and thereby reduces the incidence of adverse effects caused by sodium valproate and hence proves to be a useful combination clinically. This study has lead the basis to further investigate the various combinations of neurosteroids and valproate in the process of epileptogenesis with better side effect profile.
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