Abstract

Vanillic acid (VA) exhibited antioxidant and neuroprotective properties in some neurodegenerative disorders. So, the current study examined the neuroprotective potential of VA as an antiepileptic agent in pentylenetetrazole (PTZ)-induced epileptic rats and the prospective role of Insulin like growth factor-1 (IGF-1) and nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in this respect. Thirty male albino rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/Kg, i.p. every other day) for 14 days, and (3) PTZ + VA group: received PTZ and VA (50 mg/Kg daily for 2 weeks). The seizure score and latency were evaluated after PTZ injection. Also, the markers of oxidative stress (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), histopathological examination, the expression of glial fibrillary acidic protein (GFAP) (a marker of astrocytes) IGF-1, Nrf2, and HO-1 were assessed in the brain tissues by the end of the experiment. PTZ caused significant decrease in seizure latency and significant increase in seizure score by the end of the experiment (p < 0.01). This was associated with significant increase in MDA and GFAP with significant decrease in GSH, total antioxidant capacity (TAC) and IGF-1 in brain tissues compared to normal group (p < 0.01). On the other hand, treatment with VA caused significant attenuation in PTZ-induced seizures which was associated with significant improvement in oxidative stress markers and downregulation in GFAP and upregulation of Nrf2, HO-1 and IGF-1 in CA3 hippocampal region (p < 0.01). VA showed neuroprotective and anti-epileptic effects against PTZ-induced epilepsy which probably might be due to its antioxidant properties and upregulation of Nrf2/HO-1 pathway and IGF-1.

Highlights

  • Epilepsy is a serious neurological disorder that impacts about 1%–2% of the world’s population [1]

  • The present study aimed to investigate the impact of Vanillic acid (VA) on PTZ-induced epileptic seizure and to explore the role of nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) and Insulin like growth factor-1 (IGF-1) in this possible neuroprotective of VA in rats

  • The latency of epileptic seizures showed significantly longer values in the VA group compared to the PTZ group in trials (2, 6, 7) (p < 0.05) (Fig. 1B)

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Summary

Introduction

Epilepsy is a serious neurological disorder that impacts about 1%–2% of the world’s population [1]. Looking into the possible mechanisms of the process of epileptogenesis is mandatory to develop new agents that regulate epileptic seizures during epilepsy. The process of epileptogenesis can be replicated through kindling. Kindling is a process through which we can ignite prolonged seizures with gradually increased duration and degree of behavioral disorder. Chemical kindling via pentylenetetrazole (PTZ) is one way to induce animal models for temporal lobe epilepsy, which is the most common symptomatic refractory form of epilepsy [5]. Oxidative stress is one of the major mechanisms which initiates epilepsy and leads to its progression next to a primary brain insult [6]. Oxidative stress in neurons during epilepsy results from excessive production of reactive oxygen radicals (ROS), apoptotic, inflammatory, immune changes and dysfunction of bloodbrain barrier [7, 8]. The use of antioxidants as ascorbic acid [9], flavonoids [10], vitamin E [11], L-carnitine [12] etc., protected against epilepsy in animal models

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