Open AccessThymol 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
Author(s) -
Rasha E. Mostafa,
Azza Hassan,
Abeer Salama
Publication year - 2021
Publication title -
open access macedonian journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.288
H-Index - 17
ISSN - 1857-9655
DOI - 10.3889/oamjms.2021.6170
Subject(s) - neurotoxicity , glial fibrillary acidic protein , neuroprotection , astrocyte , monosodium glutamate , medicine , oxidative stress , pharmacology , hippocampus , hippocampal formation , endocrinology , central nervous system , toxicity , immunohistochemistry
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.