Naringin in a combined therapy with phenytoin on pentylenetetrazole-induced kindling in rats

Abstract

Phenytoin (Dilantin) is an orally active, use-dependent voltage-gated sodium channel inhibitor and is a potent, economical, and widely used anticonvulsant agent. The objective of the present study was to investigate the effect of the combined treatment of naringin (40 mg/kg and 80 mg/kg) and phenytoin on prevention of seizure attacks, development of kindling, oxidative stress, cognitive impairment, and neurochemicals in the frontal cortex, temporal cortex, and hippocampus, and morphological changes in the hippocampus. Treatment with the high dose of naringin (80 mg/kg) along with phenytoin has shown to offer protection against seizures, development of kindling, and cognition enhancement through Y-maze test and improved % conditioned avoidance response (% CAR) through pole climbing test in pentylenetetrazole (PTZ)-induced kindling model. It has also been shown to improve neurochemical balance by elevating levels of Gamma amino butyric acid (GABA) and dopamine, decreasing levels of glutamate, oxidative biomarker (malondialdehyde (MDA)), and increasing levels of antioxidants (glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total thiol and offered neuroprotection in the hippocampus. So, coadministration of naringin with phenytoin offers a potential treatment option for drug-resistant epilepsy and associated comorbidities. Interpretable research on flavonoids will support the clinical evidence for the recommendation of flavonoids as supplements with antiepileptic drugs (AEDs) for curtailing pharmacoresistant epilepsy and AED-associated comorbidities.

Keywords: GABA; Glutamate; Kindling; Naringin; Oxidative stress; Pentylenetetrazole (PTZ); Phenytoin; Y-maze.