IMR Press / JIN / Volume 21 / Issue 1 / DOI: 10.31083/j.jin2101015
Open Access Original Research
Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2/HO-1, IGF-1 signaling pathways cross talk
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1 Department of Medical Physiology, Faculty of Medicine, Mansoura University, 35516 Mansoura, Egypt
2 Department of Anatomy, College of Medicine, King Khalid University, 61421 Abha, Saudi Arabia
3 Department of Histology and Cell Biology, Faculty of Medicine, Benha University, 13518 Benha, Egypt
4 Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, 61421 Abha, Saudi Arabia
5 Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, 21955 Makah, Saudi Arabia
*Correspondence:; (Abdelaziz M. Hussein)
J. Integr. Neurosci. 2022, 21(1), 15;
Submitted: 9 July 2021 | Revised: 26 July 2021 | Accepted: 20 August 2021 | Published: 28 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

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.

PTZ-induced epilepsy
Vanillic acid
Fig. 1.
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