Sulfamethizole Attenuates Pentylenetetrazole-Induced Seizures in Mice via mTOR Inhibition

Abstract

Epilepsy affects at least 1% of the global population of all socioeconomic backgrounds. Data obtained from previous studies suggest the role of mTOR signaling in epileptogenesis. The present study aimed to investigate the hypothesis that mTOR inhibitor sulfamethizole might produce antiepileptic effects in pentylenetetrazole (PTZ)-induced kindling seizures in mice. For induction of kindling, mice were administered 40 mg/kg PTZ on alternate days for 13 days. The severity of kindling was analyzed using a seizure intensity score. Rotarod performance, actophotometer, and chimney tests were performed to check muscle coordination and locomotor functions. mTOR and IL-6 levels were measured in the brain homogenate. Histological analyses were done using hematoxylin–eosin and cresyl violet stains. Sulfamethizole was administered daily at 10 and 50 mg/kg doses. PTZ administration resulted in kindling seizures in the PTZ-veh group. In addition, mice from the PTZ-veh group showed decreased fall time in rotarod performance, reduced locomotor activity, and failed chimney tests. mTOR and IL-6 levels were also increased in the brain, along with neuronal degeneration and a decreased layer of neuronal cells in the hippocampus. Treatment with sulfamethizole at 50 mg/kg significantly ameliorated seizure intensity score, seizure latency and duration, muscle coordination, and locomotor functions compared to the PTZ-veh group. It also downregulated brain mTOR and IL-6 expression significantly. In conclusion, sulfamethizole showed antiepileptic activity against PTZ-induced kindling seizure in mice via mTOR inhibition.