Thymol Mitigates Monosodium Glutamate-Induced Neurotoxic Cerebral and Hippocampal Injury in Rats through Overexpression of Nuclear Erythroid 2-Related Factor 2 Signaling Pathway as Well as Altering Nuclear Factor-Kappa B and Glial Fibrillary Acidic Protein Expression

Rasha Mostafa; Azza Hassan; Abeer Salama

doi:10.3889/oamjms.2021.6170

Authors

Rasha Mostafa Department of Pharmacology, Medical Research Division, National Research Centre (ID: 60014618), Dokki, Cairo, Egypt https://orcid.org/0000-0002-5765-350X
Azza Hassan Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
Abeer Salama Department of Pharmacology, Medical Research Division, National Research Centre (ID: 60014618), Dokki, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2021.6170

Keywords:

Thymol, Monosodium glutamate, Neurotoxicity, Nuclear erythroid 2-related factor 2, Nuclear factor-kappa β, Glial fibrillary acidic protein

Abstract

BACKGROUND: Monosodium glutamate (MSG) is commonly used in various food industries as a flavor enhancer. MSG is reported to cause increased neurotoxicity.

AIM: The study investigates the molecular mechanisms underlying the neuroprotective effect of thymol against MSG-induced neurotoxic cerebral and hippocampal injury in rats.

MATERIALS AND METHODS: Forty rats were allocated to four Groups: I (Normal); II MSG-control (2 g/kg; i.p.); III-IV MSG + Thymol (400 and 800 mg/kg/day; p.o.). All groups were treated for 15 days.

RESULTS: MSG-control group showed a significant reduction in behavioral activity, elevated brain tissue oxidative stress, inflammatory parameters, Nuclear Erythroid 2-Related Factor 2 (Nrf2) gene upregulation, overexpression of nuclear factor-kappa β _(NF-kβ), glial fibrillary acidic protein (GFAP) along with neuronal damage in the cerebral cortex, and hippocampus. Thymol ameliorated MSG-induced brain injury through overexpression of Nrf2 gene, thus increasing the cellular defense and resulting in organized anti-oxidant and anti-inflammatory effects. Thymol improved behavioral activity and brain tissue glutathione content. Thymol also decreased brain contents of malondialdehyde, nitric oxide, tumor necrosis factor-alpha, and interleukin-6. Moreover, Thymol improved NF-kβ _and GFAP immunohistochemical expression besides histopathological picture in cerebral cortex and hippocampus as compared to MSG control rats.

CONCLUSION: These results suggest that thymol exhibits promising neuroprotective effects. The study elucidates the molecular mechanisms linking Nrf2 pathway signaling to oxidative stress, inflammation and NF-kβ _expression underlying thymol’s protection against MSG-induced neurotoxicity. The study also highlights the role of GFAP expression in MSG-induced astrocyte injury of cerebrum and hippocampus of rats and the promising protective effects of thymol in ameliorating astrocyte injury.

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