Elucidation of the Molecular Mechanism of Tempol in Pentylenetetrazol‑induced Epilepsy in Mice: Role of Gamma‑aminobutyric Acid, Tumor Necrosis Factor‑alpha, Interleukin‑1β and C‑Fos

Background: Epilepsy is a chronic neurological disorder occurred due to periodic neuronal discharge and imbalance in brain electrical activity. 4‑Hydroxy‑TEMPO (Tempol) is a membrane‑permeable radical scavenger moiety. Aim: The aim of this study is to evaluate the anticonvulsant potential of tempol against pentylenetetrazol (PTZ)‑induced seizures in mice. Materials and Methods: Convulsion was produced in the male Swiss albino mice by administration of PTZ (90 mg/kg, i.p.). Mice were pretreated with either vehicle, tempol (50, 100 and 200 mg/kg, i.p.) or diazepam (5 mg/kg). Various behavioral, biochemical, molecular, and histological parameters were evaluated. Results: Mice pretreated with tempol (100 and 200 mg/kg) showed significantly (P < 0.01 and P < 0.001) delayed‑onset on tonic‑clonic convulsion, decrease the duration of convulsions and mortality in mice. Intraperitoneal administration of PTZ resulted in significant increase in oxido‑nitrosative stress, whereas it significantly (P < 0.01 and P < 0.001) inhibited by the tempol administration. There was significant increased (P < 0.01 and P < 0.001) in the levels of brain monoamines (gamma‑aminobutyric acid [GABA] and dopamine) and Na+ K+ ATPase activity, whereas significant decreased (P < 0.01 and P < 0.001) in xanthine oxidase activity in tempol pretreated mice. PTZ‑induced up‑regulated mRNA expressions of tumor necrosis factor‑alpha, interleukin‑1 beta , and c‑Fos were significantly inhibited (P < 0.01 and P < 0.001) by tempol. It is also significantly down‑regulated (P < 0.05 and P < 0.001) immunohistochemical c‑Fos expressions. Conclusion: Pretreatment with tempol attenuates PTZ‑induced tonic‑clonic seizures via its anti‑inflammatory, anti‑oxidant and GABAergic potential.