Sodium butyrate ameliorates mitochondrial oxidative stress and alterations in membrane-bound enzyme activities in pentylenetetrazole-induced kindling rat model.

Abstract

Epilepsy is a chronic neurological disorder manifested through repeatedly recurrent unprovoked seizures. It is a debilitating neurological illness arising from exacerbated hypersynchronous neuronal firing in the brain. Among various factors, oxidative stress has been implicated in the initiation of epileptogenesis and the progression of epileptic seizures. This study investigates the neuroprotective effect of sodium butyrate in a pentylenetetrazole (PTZ)-induced kindling rat model. Male and female Wistar rats were randomly assigned into four groups for each sex. The PTZ groups were administered 40 mg/kg b.w.t intraperitoneally on alternate days for 30 days and a final single dose on the 40th day, while the sodium butyrate groups were administered along with the rat's drinking water (4 g/L). The seizure score, oxidative stress parameter, acetylcholinesterase (AChE), Na⁺-K⁺-ATPase, Ca²⁺ + Mg²⁺-ATPase, and Ca²⁺-ATPase activities were evaluated. The results showed that seizure score was significantly increased in the PTZ group, but the score was attenuated with sodium butyrate treatment. Also, mitochondrial lipid peroxidation and oxidized glutathione were elevated, while the reduction in redox potential, GSH levels, and SOD activity were detected. In addition, a decrease in AChE, Na⁺-K⁺-ATPase, Ca²⁺ + Mg²⁺-ATPase, and Ca²⁺-ATPase activities and altered hippocampal and cortical architecture were observed. The administration of sodium butyrate enhanced the antioxidant status and membrane-bound enzymes and restored the histological architecture, as shown in the study, which signifies improved neurological functions. Hence, due to its antioxidant capacity, sodium butyrate may be a possible agent for inhibiting the progression and management of epilepsy in Wistar rats.