Sodium fluoride: suggestive role in wound healing and cell proliferation with respect to regeneration
Sodium fluoride is a naturally occurring toxicant. The most common sources of sodium fluoride are municipal water, toothpastes etc. The ever increasing exposure to sodium fluoride may affect various physiological processes including regenerative capabilities. The characteristic events of regeneration include wound healing followed by cell proliferation and differentiation to replace the lost structure or tissue. Lower levels of sodium fluoride may be enhancing wound healing and cell proliferation but higher levels are detrimental for both these processes. Sodium fluoride affects wound healing by altering the expression of various proteins like fibroblast growth factors 2 and 7, Twist1 protein, matrix metalloproteinases 2 and 7, bone morphogenetic protein 7, Bcl-2, p53 etc. Sodium fluoride also influences cell division, migration and matrix synthesis by regulating the expression of bone morphogenetic proteins 2 and 3, alkaline phosphatases etc. which are markers of cell proliferation. Excessive fluoride produces oxidative stress in the cells and leads to conditions like apoptosis, cell cycle arrest and even necrosis. Thus, high levels of sodium fluoride hamper the process of cell proliferation and induce apoptosis via caspase and JNK-mediated pathway. The aim of this review is to understand the role sodium fluoride plays during wound healing and cell proliferation and its correlation with regenerative capabilities in organisms.
2. Marinho VCC, Higgins J, Logan S, Sheiham A. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2003; 1: CD002278.
3. Trattler R, Trattler S. Better health through natural healing: How to get well without drugs or surgery, 3rd edn. California, Lotus Publishing, Chichester, RJ and North Atlantic Books, 2013.
4. Sharma JD, Sohu D, Jain P. Prevalence of neurological manifestations in a human population exposed to fluoride in drinking water. Fluoride. 2009; 42(2): 127-132.
5. Levy M, Leclerc BS. Fluoride in drinking water and osteosarcoma incidence rates in the continental United States among children and adolescents. Cancer Epidemiol. 2012; 36(2): e83-e88.
6. Sun Z, Niu R, Wang B, Jiao Z, Wang J, Zhang J, et al. Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Arch Toxicol. 2011; 85: 1441-1452.
7. Lu Z, Wang S, Sun Z, Niu R, Wang J. In vivo influence of sodium fluoride on sperm chemotaxis in male mice. Arch Toxicol. 2014; 88: 533-539.
8. Bhatnagar M, Rao P, Saxena A, Bhatnagar R, Meena P, Barbar S, et al. Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride. 2006; 39(4): 280-284.
9. Denes J, Gabris K, Denes Z. Effect of various mouthwashes on wound healing after tooth extraction. Fogorv Sz. 1994; 87(8): 237-243.
10. Biller T, Yosipovitch Z, Gedalia I. Effect of topical application of fluoride on the healing rate of experimental calvarial defects in rats. J Dent Res. 1977; 56(1): 53-56.
11. Arakawa Y, Bhawal UK, Ikoma T, Kimoto K, Kuroha K, Kubota T, et al. Low concentration fluoride stimulates cell motility of epithelial cells in vitro. Biomed Res. 2009; 30(5): 271-277.
12. He D, Bhawal UK, Hamada N, Kuboyama N, Abiko Y, Arakawa H. Low level fluoride stimulates epithelial-mesenchymal interaction in oral mucosa. J Hard Tissue Biol. 2013; 22(1): 59-66.
13. Alhijazi AY, Neamah AD. Expression of VEGF and BMP7 in bone healing after topical, systemic fluoride application (experimental study in rats). Int Res J Natural Sci. 2014; 2(1): 52-68.
14. Fernandes MS, Martins GM, Shimoraha LM, Iano FG, Yanai MM, Cestari TM, et al. Fluoride effect on the process of alveolar bone repair in rats: evaluation of activity of MMP-2 and 9. RSBO. 2012; 9(3): 229-237.
15. Li KQ, Jia SS, Ma M, Shen HZ, Xu L, Liu GP, et al. Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro. Braz J Med Biol Res. 2016; 49(8): e5291.
16. Azarpira MR, Emami MJ, Torabinejad S, Abdinejad F, Azarpira N, Mehrabani D. Effect of sodium fluoride on fracture healing in experimental rabbits. J Applied Animal Res. 2008; 34(2): 173-177.
17. Wei Y, Wu Y, Zeng B, Zhang H. Effects of sodium fluoride treatment in vitro on cell proliferation, BMP-2 and BMP-3 expression in human osteosarcoma MG-63 cells. Biol Trace Elem Res. 2014; 162(1-3): 18-25.
18. Fu X, Xie F, Dong P, Li Q, Yu G, Xiao R. High-dose fluoride impairs the properties of human embryonic stem cells via JNK signaling. PLOS One. 2016; 11(2): e0148819.
19. Susheela AK, Bhatnagar M. Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and antioxidants. Mol Cell Biochem. 2002; 234: 335-340.
20. Jha SK, Mishra VK, Sharma DK, Damodaran T. Fluoride in the environment and its metabolism in humans. Rev Environ Contam Toxicol. 2011; 211: 121-142.
21. Liu XL, Li CC, Liu KJ, Cui CY, Zhang YZ, Liu Y. The influence of fluoride on the expression of inhibitors of Wnt/β-catenin signaling pathway in rat skin fibroblast cells. Biol Trace Elem Res. 2012; 148(1): 117-121.
22. Oquro A, Cervenka J, Horii K. Effect of sodium fluoride on growth of human diploid cells in culture. Pharmacol Toxicol. 1990; 67(5): 411-414.
23. Song C, Cao X, Yang Z, Guo S, Shang Z. Fluoride-induced cell cycle arrest, apoptosis, and DNA damage in TM3 mouse Leydig cells. Fluoride. 2013; 46(4): 218-223.
24. Tatin F, Grise F, Reuzeau E, Genot E, Moreau V. Sodium fluoride induces podosome formation in endothelial cells. Biol Cell. 2010; 102: 489-498.
25. Song JS, Lee HY, Lee E, Hwang HJ, Kim JH. Cytotoxicity and apoptosis induction of sodium fluoride in human promyelocytic leukemia (HL-60) cells. Environ Toxicol Pharmacol. 2002; 11: 85-91.
26. Zhang M, Wang A, Xia T, He P. Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kB in primary cultured rat hippocampal neurons. Toxicol Lett. 2008; 179: 1-5.
27. Manivannan J, Sinha S, Ghosh M, Mukherjee A. Evaluation of multi-endpoint assay to detect genotoxicity and oxidative stress in mice exposed to sodium fluoride. Mutat Res. 2013; 751: 59-65.
28. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004; 266: 37-56.
29. Chouhan S, Flora SJS. Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data. Toxicology. 2008; 254: 61-70.
30. Podder S, Chattopadhyay A, Bhattacharya S, Ray MR. Differential in vivo genotoxic effects of lower and higher concentrations of fluoride in mouse bone marrow cells. Fluoride. 2008; 41: 301-307.
31. Yan X, Feng C, Chen Q, Li W, Wang H, Lv L, et al. Effects of sodium fluoride treatment in vitro on cell proliferation, apoptosis and caspase-3 and caspase-9 mRNA expression by neonatal rat osteoblasts. Arch Toxicol. 2009; 83(5): 451-458.
32. Song GH, Wang RL, Chen ZY, Zhang B, Wang HL, Liu ML, et al. Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice. J Physiol Biochem. 2014; 70(3): 761-768.
33. Hasan HA, Abdel-Aziz AF. Evaluation of free-radical scavenging and anti-oxidant properties of black berry against fluoride toxicity in rats. Food Chem Toxicol. 2010; 48: 1999-2004.
34. Podder S, Ghoshal N, Banerjee A, Ganguly B, Upadhyy R, Chatterjee A. Interaction of DNA-lesions induced by sodium fluoride and radiation and its influence in apoptotic induction in cancer cell lines. Toxicol Rep. 2015; 2: 461-471.
35. Jachimczak D, Skotarczak B. The effect of fluorine and lead ions on the chromosomes of human leukocytes in vitro. Genet Pol. 1978; 19: 353-357.
36. Chaurasia OP, Kumari C, Sangita A. Genotoxic effects of ground water salts rich in fluoride. Cytologia (Tokyo). 2007; 72: 141-144.
37. Barzilai A. The contribution of the DNA damage response to neuronal viability. Antioxid Redox Signal. 2007; 9: 211-218.
38. Jothiramajayam M, Sinha S, Ghosh M, Nag A, Jana A, Mukherjee A. Sodium fluoride promotes apoptosis by generation of reactive oxygen species in human lymphocytes. J Toxicol Environ Health A. 2014; 77(21): 1269-1280.
39. Liang S, Nie Z, Zhao M, Niu Y, Shin K, Cui X. Sodium fluoride exposure exerts toxic effects on porcine oocyte maturation. Sci Reports. 2017; 7: 17082.
40. Kuang P, Deng H, Cui H, Chen L, Guo H, Fang J, et al. Suppressive effects of sodium fluoride on cultured splenic lymphocyte proliferation in mice. Oncotarget. 2016; 7(38): 61905-61915.
41. Kuang P, Deng H, Cui H, Chen L, Fang J, Zuo Z, et al. Sodium fluoride (NaF) causes toxic effects on splenic development in mice. Oncotarget. 2017; 8(3): 4703-4717.
42. Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010; 188(2): 319-333.
43. Agalakova NI, Gusev GP. Moleular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biol. 2012; ID 403835.
44. Yadav M, Buch P, Desai I, Balakrishnan S. Exogenous administration of EGF augments nucleic acid biosynthesis and cell proliferation in the regenerating tail of wall lizard. Eur J Exp Bio. 2014; 4(2): 113-123.
45. Suresh B, Hiradar PK. Fluoride induced changes in certain metabolites during tail regeneration in the gekkonid lizard, Hemidactylus flaviviridis. Fluoride. 1990; 23(2): 92-97.
46. Williams J. The effects of fluoride ions on neuromuscular activity and regeneration in Dugesia tigrina. Georgia J Sci. 2017; 75(2): 1-7.
47. Devkar RV, Mankodi PC, Ramachandran AV. Ameliorative action of melatonin over fluoride induced retarded regenerative performance of caudal fin of Poecilia latepinna. J Curr Sci. 2008; 12(2): 395-399.
48. Babich GL, Foret JE. Effects of dibutyryl cyclic AMP and related compounds on newt limb regeneration blastemas in vitro. Onco. 1973; 28: 89-95.
49. Foret JE, Babich GL. Effects of dibutyryl cyclic AMP and related compounds on newt limb regeneration blastemas in vitro. Onco. 1973; 28: 83-88.
50. Li KQ, Jia SS, Ma M, Shen HZ, Xu L, Liu GP, et al. Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro. Braz J Med Biol Res. 2016; 49(8): 1-8.
51. Hall, BK. Diversity of bone as a tissue and as an organ. In: Bones and cartilage: developmental and evolutionary skeletal biology. USA, Academic Press, 2003: 417-418.
52. Harland, RM. A new view of embryo development and regeneration. Sci. 2018; 360(6392): 967-968.
53. Zhang Y, Xie L, Li X, Chai L, Chen M, Kong X, et al. Effects of fluoride on morphology, growth, development, and thyroid hormone of Chinese toad (Bufo gargarizans) embryos. Environ Mol Mutagen. 2018; 59(2): 123-133.
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