Fluoride Action Network

Abstract

Excess fluoride intake has been linked with various pathological conditions. The objective of the present study was to understand the role of fluoride in neurotoxic, neuroinflammatory, and neurodegenerative changes in the brain tissue of Wistar rats. Wistar rats were fed with water containing 20–100 ppm (ppm) sodium fluoride (NaF). An array of neurotransmitters (acetylcholine, dopamine, epinephrine, norepinephrine, serotonin, histamine, and glutamate) expression levels were estimated with respect to different fluoride concentrations. Additionally, its effect on the expression levels of specific neuroinflammatory markers (iNOS, COX-2, TNF-?, PKC, VEGF, and HSP-70) in brain tissues of Wister rats was assessed. An increase in NaF concentration resulted in increased fluoride deposition in the brain which in turn caused increase levels of epinephrine, histamine, serotonin, and glutamate and decreased levels of norepinephrine, acetylcholine, and dopamine in a dose-dependent manner. Tissue fluoride levels of the hippocampus, neocortex, cerebellum, spinal cord, and sciatic nerve increased significantly in fluoride fed rats. Transmission electron microscopy in the experimental animals revealed axon deterioration, myelin sheath degeneration, and dark cells with scanty cytoplasm in the spinal cord and sciatic nerve. Additionally, vacuolated swollen mitochondria were observed in the neocortex, hippocampus, and cerebellum. Results suggest excess fluoride intake modulates a set of biological marker and promote neuroinflammatory and neurodegenerative condition in Wister rats. Therefore, we conclude that the accumulation of NaF alters the neurological function which leads to neurodegenerative disorders.

*Original abstract online at https://link.springer.com/article/10.1007%2Fs12011-020-02362-x

References

  1. Varner JA, Jensen KF, Horvath W, Isaacson RL (1998 Feb 16) Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Res 784(1–2):284–298. CAS  Article  Google Scholar
  2. Mahaboob Basha P, Saumya SM (2013 Apr) Suppression of mitochondrial oxidative phosphorylation and TCA enzymes in discrete brain regions of mice exposed to high fluoride: amelioration by Panax ginseng (Ginseng) and Lagerstroemia speciosa (Banaba) extracts. Cell Mol Neurobiol 33(3):453–464. CAS  Article  Google Scholar
  3. Kinawy AA (2019) Synergistic oxidative impact of aluminum chloride and sodium fluoride exposure during early stages of brain development in the rat. Environ Sci Pollut Res Int 26(11):10951–10960. CAS  Article  Google Scholar
  4. Shivarajashankara YM, Shivashankara AR, Bhat PG, Rao SM, Rao SH (2002) Histological changes in the brain of young fluoride-intoxicated rats. Fluoride. 35(1):12–21. CAS  Google Scholar
  5. McPherson CA, Zhang G, Gilliam R et al (2018) An evaluation of neurotoxicity following fluoride exposure from gestational through adult ages in long-Evans hooded rats. Neurotox Res 34(4):781–798. CAS  Article  Google Scholar
  6. Kari HP, Davidson PP, Kohl HH, Kochhar MM (1978 Jun) Effects of ketamine on brain monoamine levels in rats. Res Commun Chem Pathol Pharmacol 20(3):475–488.CAS  PubMed  Google Scholar
  7. Narayanaswamy M, Piler MB (2010 Jan) Effect of maternal exposure of fluoride on biometals and oxidative stress parameters in developing CNS of rat. Biol Trace Elem Res 133(1):71–82. CAS  Article  Google Scholar
  8. Valdez-Jiménez L, Soria Fregozo C, Miranda Beltrán ML, Gutiérrez Coronado O, Pérez Vega MI (2011) Effects of the fluoride on the central nervous system. Neurologia. 26(5):297–300. Article  Google Scholar
  9. Vester H, Huber-Lang MS, Kida Q, Scola A, van Griensven M, Gebhard F, Nüssler AK, Perl M (2014) The immune response after fracture trauma is different in old compared to young patients. Immun Ageing 11(1):20. Article  Google Scholar
  10. Dekker AB, Krijnen P, Schipper IB (2016) Predictive value of cytokines for developing complications after polytrauma. World J Crit Care Med 5(3):187–200. Article  Google Scholar
  11. Perera T, Ranasinghe S, Alles N, Waduge R (2018) Effect of fluoride on major organs with the different time of exposure in rats. Environ Health Prev Med 23(1):17. Article  Google Scholar
  12. Yan N, Liu Y, Liu S, Cao S, Wang F, Wang Z, Xi S (2016) Fluoride-induced neuron apoptosis and exvpressions of inflammatory factors by activating microglia in rat brain. Mol Neurobiol 53(7):4449–4460. CAS  Article  Google Scholar
  13. Natarajan K, Abraham P, Kota R, Isaac B (2018) NF-?B-iNOS-COX2-TNF ? inflammatory signaling pathway plays an important role in methotrexate induced small intestinal injury in rats. Food Chem Toxicol 118:766–783.CAS  Article  Google Scholar
  14. Basha PM, Rai P, Begum S (2011 Sep) Evaluation of fluoride-induced oxidative stress in rat brain: a multigeneration study. Biol Trace Elem Res 142(3):623–637. CAS  Article  Google Scholar
  15. Choi AL, Sun G, Zhang Y, Grandjean P (2012 Oct) Developmental fluoride neurotoxicity: a systematic review and meta-analysis. Environ Health Perspect 120(10):1362–1368. CAS  Article  Google Scholar

Acknowledgments

The authors would like to thank Prof. Pratap K. Reddy, Dr. Praveen K. Kumar, and the technical staff of Dept. of Zoology, Osmania University, Hyderabad, India, for their kind patronage. PYR would like to acknowledge the University Grants Commission for awarding Teacher Fellowship during the 10th plan period.

Author information

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Contributions

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

Corresponding author

Correspondence to Varun Kumar Sharma.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

The study protocol was approved by the Animal Ethics committee (CPCSEA NO: 383/01/a/CPCSE) of the Department of Zoology, Osmania University, Hyderabad, India.