Neuroprotective effect of Nrf2 activator dimethyl fumarate, on the hippocampal neurons in chemical kindling model in rat

Abstract

Background: Nuclear factor erythroid-2 related factor 2 (Nrf2) is a transcription factor, which activates the anti-oxidative stress response pathway. In epilepsy, oxidative stress is one of the key factors in the progression of the disease. So, the neuroprotective role of dimethyl fumarate (DMF), a Nrf2 pathway activator was explored in pentylenetetrazole (PTZ) induced kindling model of epilepsy in rats.

Methods: Male Wistar rats were subjected to different doses of DMF (15, 30, 60 mg/kg) to evaluate the effect on the PTZ induced kindling in rats. Seizure scoring, the percentage of animals kindled, histopathological analysis of hippocampus and biochemical estimation were done to study the effect of DMF on PTZ induced oxidative stress in rats.

Key findings: The number of kindled animals in the DMF 60 mg/kg treatment group (25%) was less in comparison to corn oil + PTZ control group (62.5%). The histopathological analysis of the hippocampus revealed a significant (p = 0.003) decrease in neuronal damage in DMF 60 mg/kg group as compared to corn oil + PTZ control group. The DMF 60 mg/kg treatment improved the level of antioxidants: glutathione peroxidase (GPx), superoxide dismutase (SOD), reduced glutathione (GSH) and reduced the lipid peroxidation as compared to corn oil + PTZ group.

Conclusions: DMF has demonstrated the neuroprotective effect in PTZ induced kindling model of epilepsy. This can prove advantageous in the development of new treatment strategies for epilepsy.

Keywords: Dimethyl fumarate (DMF); Neuroprotection; Nrf2; PTZ kindling.