To Explore The Neuroprotective Effect Of Apocynin Against Pentylenetetrazole Kindling Epilepsy-Induced Comorbidities In Mice

Abstract

Epilepsy is a neurological disease that transpires due to the unusual synchronized neuronal discharge within the CNS, which drives repetitious unprovoked seizures. NADPH oxidase is a complex enzyme accountable for ROS production, neurodegeneration, neurotoxicity, memory impairment, vitiates normal cellular processes, long term potentiation, and thus implicated in the pathogenesis of epilepsy. Therefore, the present study was sketched to examine the neuroprotective effect of apocynin, NADPH oxidase inhibitor in PTZ kindling epilepsy, and induced comorbidities in mice. Mice (either sex) were given PTZ (35 mg/kg i.p.) every other day up to 29 days and a challenge test was executed on the 33rd day. Pretreatment with apocynin (25, 50, and 100 mg/kg i.p.) was initiated from 1st day and resumed till 33rd day. Rotarod and OFT were performed on 1st, 10th, 20th, and 30th days of the study. Animals were tutored on MWM from 30th to 33rd day and the retention was registered on 34th day. TST and EPM were sequentially performed on the 32nd and 33rd day of the study. On the 34th day, animals were sacrificed and brains of the animals were isolated to conduct biochemical (LPO, GSH, nitrite, SOD, catalase) estimation. NADPH oxidase activation due to chronic PTZ treatment resulted in GTCS, enhanced oxidative stress, remodeled the level of neurotransmitters, and resulted in comorbidities (anxiety, depression, and memory impairment). Pretreatment with apocynin significantly restricted the PTZ induced seizure severity, ROS production, neurotransmitter alteration, and comorbid conditions by inhibiting the NADPH oxidase enzyme.