Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy

Aims: Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Materials and methods: Male Wistar rats received 30 mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100 mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Key findings: Kindling was developed 34.18 +/- 1.54 days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100 mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. Significance: Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/ molecular mechanism(s) underlying the action of ferulic acid. (C) 2016 Elsevier Inc. All rights reserved.