Effect of fenofibrate on plasma level of BDNF and brain oxidative stress markers in pentylenetetrazole-induced kindling seizure in mice

Abstract

Introduction : The neuroprotective effect and pleiotropic functions of PPARα agonists (peroxisome proliferator activated receptor-alpha) such as fenofibrate and bezafibrate have been demonstrated by the previous studies. The current study evaluated the antiepileptic effects and neuroprotective functions of fenofibrate in pentylenetetrazole (PTZ)-induced kindling seizure in mice. Materials and Methods : Adult male NMRI mice were randomly assigned into three groups (n=8): Control, untreated kindled mice and fenofibrate-treated kindled animals. Repeated intraperitoneal injections of PTZ (45 mg/kg) once every 48 hours were used to develop the kindling seizure for 21 days. Treated mice were administered orally fenofibrate at doses of 30 mg/kg/day. Plasma level of brain-derived neurotrophic factor (BDNF), brain level of malondialdehyde (MDA) and histopathological changes were evaluated at termination of the study. Results: Fenofibrate administration considerably improved the seizure latency in treated kindled mice. Fenofibrate significantly ( P <0.05) decreased plasma BDNF level in treated kindled mice (12.06±0.08 ng/mL) compared to PTZ group (13.43±0.20 ng/mL). Treatment with fenofibrate significantly ( P <0.05) decreased MDA level of brain by 68% in treated kindled mice compared to PTZ group. In addition, fenofibrate improved the histopathological damages in treated kindled animals. Conclusion: Fenofibrate ameliorated the plasma level of BDNF and brain level of MDA accompanied with the brain histopathological damages in kindling seizure in mice that might be associated to improving the seizure behaviors.