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Review
. 2020 Apr;94(4):1051-1069.
doi: 10.1007/s00204-020-02687-5. Epub 2020 Mar 9.

Principles of fluoride toxicity and the cellular response: a review

Nichole R Johnston  1 , Scott A Strobel  2   3
Affiliations
Review

Principles of fluoride toxicity and the cellular response: a review

Nichole R Johnston et al. Arch Toxicol. 2020 Apr.

Abstract

Fluoride is ubiquitously present throughout the world. It is released from minerals, magmatic gas, and industrial processing, and travels in the atmosphere and water. Exposure to low concentrations of fluoride increases overall oral health. Consequently, many countries add fluoride to their public water supply at 0.7-1.5 ppm. Exposure to high concentrations of fluoride, such as in a laboratory setting often exceeding 100 ppm, results in a wide array of toxicity phenotypes. This includes oxidative stress, organelle damage, and apoptosis in single cells, and skeletal and soft tissue damage in multicellular organisms. The mechanism of fluoride toxicity can be broadly attributed to four mechanisms: inhibition of proteins, organelle disruption, altered pH, and electrolyte imbalance. Recently, there has been renewed concern in the public sector as to whether fluoride is safe at the current exposure levels. In this review, we will focus on the impact of fluoride at the chemical, cellular, and multisystem level, as well as how organisms defend against fluoride. We also address public concerns about fluoride toxicity, including whether fluoride has a significant effect on neurodegeneration, diabetes, and the endocrine system.

Keywords: Cell stress; Fluoride; Metal; Toxicity.

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Conflict of interest statement

Conflict of interest: The authors declare that they have no conflict of interest.

Figures

Figure 1:
Figure 1:
Global distribution of fluoride. Shown here are areas with (A) <1.5 ppm fluoride in the groundwater (purple), (B) mining of fluoro-compounds (blue squares -fluorspar, brown circles – fluorapatite, green triangles - topaz, and black diamonds - cryolite), (C) percent of the population given government-regulated fluoridated water (light teal – 0–33%, teal – 34–67%, black – 68–100% of population), and (D) endemic fluoride toxicity (red) [Unicef 1999, WHO 2004, Gupta and Ayoob 2016, British Geological Survey, and the USGS Database].
Figure 2:
Figure 2:
Fluoride interactions in vitro. (A) Fluoride is the most similar in terms of size and charge to hydroxide, but has a much higher affinity for metals. (B) unit cells of crystallized hydroxyapatite (Ca5(PO4)3OH) and fluorapatite (Ca5(PO4)3F) [Minerology Database]. (C) Crystal structures of fluoride bound to urease and (D) phosphoserine phosphatase. Structures were generated on PyMOL using RCSB PDB (C) 4GOA and (D) 1L7N.
Figure 3:
Figure 3:
Intracellular fluoride toxicity. General scheme of downstream organelle damage after prolonged exposure to high fluoride, conserved across eukaryotes.
Figure 4:
Figure 4:
Global network of cellular processes involved in the resistance of bacteria to fluoride. (A) Conserved molecular functions and cellular components of (A) genes regulated by the fluoride riboswitch, as reported by Weinberg et al. 2010, and (B) altered genes in fluoride resistant bacteria (Zhu et al. 2012; Liao et al. 2015; 2016; Ma et al. 2016; Liu et al. 2017). Genes were converted to their E. coli homologs, and duplicates were discarded. Data was analyzed on Cytoscape using ClueGO. Node size corresponds with the number of genes per category, and similar colored nodes denote a similar cluster in function.
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References

    1. Aaron JE, de Vernejoul MC, Kanis JA (1991) The effect of sodium fluoride on trabecular architecture. Bone 12:307–310. 10.1016/8756-3282(91)90015-B - DOI - PubMed
    1. Abdelaleem MM, El-Tahawy NFG, Abozaid SMM, Abdel-Hakim SA (2018) Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: light and electron microscopic study. Endocr Regul 52:59–68. 10.2478/enr-2018-0007 - DOI - PubMed
    1. Adamek E, Palowska-Goral K, Bober K (2005) In vitro and in vivo effects of fluoride ions on enzyme activity. Ann Acad Med Stetin 51:69–85. - PubMed
    1. Agalakova NI, Gusev GP (2011) Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. Int Sch Res Not 2012:16 10.5402/2012/403835 - DOI
    1. Ainsworth NJ (1933) Mottled teeth. Brit Dent J 55:233–250.

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