Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of a-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.

• Baxter PS, Hardingham GE (2016) Adaptive regulation of the brain’s antioxidant defences by neurons and astrocytes. Free Radic Biol Med 100:147–152. https://doi.org/10.1016/j.freeradbiomed.2016.06.027

  Article  CAS  PubMed  PubMed Central  Google Scholar

• Cheng M, Yuan C, Ju Y et al (2024) Quercetin attenuates oxidative stress and apoptosis in brain tissue of APP/PS1 double transgenic AD mice by regulating Keap1/Nrf2/HO-1 pathway to improve cognitive impairment. Behav Neurol 2024:5698119. https://doi.org/10.1155/2024/5698119

  Article  PubMed  PubMed Central  Google Scholar

• Cuadrado A, Rojo AI, Wells G et al (2019) Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov 18(4):295–317. https://doi.org/10.1038/s41573-018-0008-x

  Article  CAS  PubMed  Google Scholar

• Dec K, ?ukomska A, Maciejewska D et al (2017) The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System. Biol Trace Elem Res 177(2):224–234. https://doi.org/10.1007/s12011-016-0871-4

  Article  CAS  PubMed  Google Scholar

• Dondossola ER, Pacheco SD, Visentin SC et al (2022) Prolonged fluoride exposure alters neurotransmission and oxidative stress in the zebrafish brain. Neurotoxicology 89:92–98. https://doi.org/10.1016/j.neuro.2022.01.008

  Article  CAS  PubMed  Google Scholar

• Johnston NR, Strobel SA (2020) Principles of fluoride toxicity and the cellular response: a review. Arch Toxicol 94(4):1051–1069. https://doi.org/10.1007/s00204-020-02687-5

  Article  CAS  PubMed  PubMed Central  Google Scholar

• Khandare AL, Gourineni SR, Validandi V (2017) Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India. Environ Monit Assess 189(11):579. https://doi.org/10.1007/s10661-017-6288-5

  Article  CAS  PubMed  Google Scholar

• Kocak Y, Oto G, Huyut Z et al (2023) Effects of fluoride on oxidative DNA damage, nitric oxide level, lipid peroxidation and cholinesterase enzyme activity in a rotenone-induced experimental Parkinson’s model. Neurol Res 45(11):979–987. https://doi.org/10.1080/01616412.2023.2257452

  Article  CAS  PubMed  Google Scholar

• Kumar S, Swamy RS, Bhushan R et al (2024) Molecular and immunohistochemical alterations in fluoride-induced neurological impediment in adult rats. J Trace Elem Med Biol 86:127511. https://doi.org/10.1016/j.jtemb.2024.127511

  Article  CAS  PubMed  Google Scholar

• Kustrimovic N, Marino F, Cosentino M (2019) Peripheral immunity, immunoaging and neuroinflammation in Parkinson’s disease. Curr Med Chem 26(20):3719–3753. https://doi.org/10.2174/0929867325666181009161048

  Article  CAS  PubMed  Google Scholar

• Lai C, Chen Q, Ding Y et al (2020) Emodin protected against synaptic impairment and oxidative stress induced by fluoride in SH-SY5Y cells by modulating ERK1/2/Nrf2/HO-1 pathway. Environ Toxicol 35(9):922–929. https://doi.org/10.1002/tox.22928

  Article  CAS  PubMed  Google Scholar

• Lee HJ, Suk JE, Patrick C et al (2010) Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285(12):9262–9272. https://doi.org/10.1074/jbc.M109.081125

  Article  CAS  PubMed  PubMed Central  Google Scholar

• Loria F, Vargas JY, Bousset L et al (2017) ?-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading. Acta Neuropathol 134(5):789–808. https://doi.org/10.1007/s00401-017-1746-2

  Article  CAS  PubMed  Google Scholar

• Lou DD, Guan ZZ, Liu YJ et al (2013) The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain. Arch Toxicol 87(3):449–457. https://doi.org/10.1007/s00204-012-0942-z

  Article  CAS  PubMed  Google Scholar

• Meade RM, Fairlie DP, Mason JM (2019) Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles. Mol Neurodegener 14(1):29 Published 2019 Jul 22. https://doi.org/10.1186/s13024-019-0329-1

  Article  CAS  PubMed  PubMed Central  Google Scholar

• Mondal P, Shaw P, Dey Bhowmik A et al (2021) Combined effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) brain: alterations in stress marker and apoptotic gene expression. Chemosphere 269:128678. https://doi.org/10.1016/j.chemosphere.2020.128678

  Article  CAS  PubMed  Google Scholar

• Fang L, Xia C, Li S, Xiao L, Jin H (2021) Osteosclerosis and osteoporosis – different bone impairments from high bone turnover of skeletal fluorosis: a case study on the femoral head. Pathology Published online April 3. https://doi.org/10.1016/j.pathol.2020.11.014

• Oyagbemi AA, Adebiyi OE, Adigun KO et al (2020) Clofibrate, a PPAR-? agonist, abrogates sodium fluoride-induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba-1/anti-calbindin signaling pathways. Environ Toxicol 35(2):242–253. https://doi.org/10.1002/tox.22861

  Article  CAS  PubMed  Google Scholar

• Panneerselvam L, Raghunath A, Sundarraj K, Perumal E (2019) Acute fluoride exposure alters myocardial redox and inflammatory markers in rats. Mol Biol Rep 46(6):6155–6164. https://doi.org/10.1007/s11033-019-05050-9

  Article  CAS  PubMed  Google Scholar

• Raj A, Kaushal A, Datta I (2022) Impact of monomeric and aggregated wild-type and A30P/A53T double-mutant ?-synuclein on antioxidant mechanism and glutamate metabolic profile of cultured astrocytes. J Neurosci Res 100(2):681–706. https://doi.org/10.1002/jnr.24994

  Article  CAS  PubMed  Google Scholar

• Ran LY, Xiang J, Zeng XX et al (2021) Integrated transcriptomic and proteomic analysis indicated that neurotoxicity of rats with chronic fluorosis may be in mechanism involved in the changed cholinergic pathway and oxidative stress. J Trace Elem Med Biol 64:126688. https://doi.org/10.1016/j.jtemb.2020.126688

  Article  CAS  PubMed  Google Scholar

• Reddy YP, Tiwari S, Tomar LK et al (2021) Fluoride-Induced Expression of Neuroinflammatory Markers and Neurophysiological Regulation in the Brain of Wistar Rat Model. Biol Trace Elem Res 199(7):2621–2626. https://doi.org/10.1007/s12011-020-02362-x

  Article  CAS  PubMed  Google Scholar

• Sharma C, Suhalka P, Bhatnagar M (2018) Curcumin and resveratrol rescue cortical-hippocampal system from chronic fluoride-induced neurodegeneration and enhance memory retrieval. Int J Neurosci 128(11):1007–1021. https://doi.org/10.1080/00207454.2018.1458727

  Article  CAS  PubMed  Google Scholar

• Song C, Heping H, Shen Y et al (2020) AMPK/p38/Nrf2 activation as a protective feedback to restrain oxidative stress and inflammation in microglia stimulated with sodium fluoride. Chemosphere 244:125495. https://doi.org/10.1016/j.chemosphere.2019.125495

  Article  CAS  PubMed  Google Scholar

• Soto C, Pritzkow S (2018) Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat Neurosci 21(10):1332–1340. https://doi.org/10.1038/s41593-018-0235-9

  Article  CAS  PubMed  PubMed Central  Google Scholar

• Tang Z, Lai CC, Luo J et al (2021) Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH-SY5Y cells. J Biochem Mol Toxicol 35(4):e22705. https://doi.org/10.1002/jbt.22705

  Article  CAS  PubMed  Google Scholar

• Uruno A, Yamamoto M (2023) The KEAP1-NRF2 System and Neurodegenerative Diseases. Antioxid Redox Signal 38(13–15):974–988. https://doi.org/10.1089/ars.2023.0234

  Article  CAS  PubMed  Google Scholar

• Wang C, Liang LL, Ye L et al (2021) Expression of GFAP, ?-tubulin III and synaptophsin and intervention effects of chondroitin sulfate in brain of rats with chronic fluorosis[J]. Chin J Endemiol 40(10):781–789

  Google Scholar

• Yadav KK, Kumar S, Pham QB et al (2019) Fluoride contamination, health problems and remediation methods in Asian groundwater: a comprehensive review. Ecotoxicol Environ Saf 182:109362. https://doi.org/10.1016/j.ecoenv.2019.06.045

  Article  CAS  PubMed  Google Scholar

• Zhao Y, Li Y, Wang J, Manthari RK, Wang J (2018) Fluoride induces apoptosis and autophagy through the IL-17 signaling pathway in mice hepatocytes. Arch Toxicol 92(11):3277–3289. https://doi.org/10.1007/s00204-018-2305-x

  Article  CAS  PubMed  Google Scholar

• Zhao WP, Zhu SQ, Yin ZH et al (2026) Short-chain fatty acids alleviated fluoride-induced neuroinflammation via the gut-brain axis in rats. Environ Pollut 390:127503. https://doi.org/10.1016/j.envpol.2025.127503

  Article  CAS  PubMed  Google Scholar

• Zhou J, Sun D, Wei W (2023) Necessity to Pay Attention to the Effects of Low Fluoride on Human Health: an Overview of Skeletal and Non-skeletal Damages in Epidemiologic Investigations and Laboratory Studies. Biol Trace Elem Res 201(4):1627–1638. https://doi.org/10.1007/s12011-022-03302-7

  Article  CAS  PubMed  Google Scholar

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