Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy
Yildiz, Mustafa Onur, Celik, Hamit, Caglayan, Cuneyt, Kandemir, Fatih Mehmet, Gur, Cihan, Bayav, Ibrahim, Genc, Aydin, Kandemir, Ozge
Fluoride is an element with toxic properties and has been proven to have some adverse effects on many soft tissues, including brain tissue. This study aims to evaluate the protective effects of hesperidin on sodium fluoride (NaF)-induced neurotoxicity in rats by biochemical and molecular methods. The animals were randomly divided into five groups of seven rats each as Control, hesperidin, NaF (600 ppm), NaF + hesperidin (100 mg/kg, b.w.), and NaF + hesperidin (200 mg/kg, b.w.), respectively; orally for two weeks. Hesperidin reduced lipid peroxidation and increased activities of SOD, CAT and GPx and levels of GSH in NaF-induced brain tissue. Hesperidin also showed anti-inflammatory and anti-autophagic effects by decreasing levels of NF-kappa B, IL-1B, TNF-alpha, Beclin-1, LC3A, and LC3B in NaF-induced brain tissue. Moreover, hesperidin was able to down-regulate the mRNA transcript levels of apoptosis and endoplasmic reticulum stress markers such as caspase-3, Bax, Bcl-2, PERK, IRE1, ATF6, and GRP78 in NaF-induced neurotoxicity. Hesperidin also reduced the adverse effects caused by NaF by modulating the PI3K/Akt/mTOR signaling pathway. These results demonstrate that hesperidin exhibits neuroprotective effects against NaF-induced neurotoxicity in rats by ameliorating inflammation, apoptosis, autophagy, and endoplasmic reticulum stress.
- Journal
- NEUROTOXICOLOGY
- Year
- 2022
- Volume
- 90
- Pages
- 197-204
- ISSN
- 0161-813X
- eISSN
- 1872-9711
- DOI
- 10.1016/j.neuro.2022.04.002
- WoS UID
- WOS:000793681700002