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A Rat Experimental Study of the Relationship Between Fluoride Exposure and Sensitive Biomarkers

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Abstract

Chronic excessive fluoride exposure impairs human health and damages not only the skeletal system and the teeth but also the soft tissues such as the brain, liver, kidneys, pancreas and spinal cord. However, there is limited research regarding the exposure levels and sensitive biomarkers. This study was aimed to establish the relationship between fluoride exposure and sensitive biomarkers. Ninety-six rats were randomly divided into six groups, with each group exposed to 0, 2, 4, 8, 16 and 32 mg NaF/(kg.bw), respectively. Correlation analysis of the exposure levels, the tissue distributions and the effects was done, and the possible mathematical relationship between the exposure and sensitive biomarkers is discussed. Our findings revealed that the level of serum fluoride can serve as one of the sensitive indicators to reflect the ex-exposure levels (in the present article, ex-exposure means the fluoride exposure pathway from the outside, which differs from the burden of the organism). Furthermore, an equation determining the external exposure dose of serum fluoride was obtained by fitting the coefficient 0.901. Simultaneously, enzyme levels were closely compared with the burden of the tissue, which showed that the activities of alkaline phosphatase significantly correlated with serum fluoride levels (R 2 = −0.259, p < 0.05), as well as with the fluoride levels of the lung (R 2 = 0.463, ρ < 0.01), the thymus (R 2 = 0.429, ρ < 0.05) and the ovary/testicle (R 2 = 0.685, ρ < 0.01). Results suggested that excessive fluoride exposure might affect reproduction by altering the activities of alkaline phosphatase. In addition, some indicators related to immunity and calcium absorption exhibited sensitivity to tissue burden, among which activating transcriptional factor 4 (ATF4), an important indicator involved in bone metabolism, was found sensitive to the ex-exposure level. These findings highlight the gap between health effects in epidemiology research and the total intake amount of fluoride from the environment. This study presents a novel insight into the method of establishing the relationship between fluoride exposure and sensitive biomarkers.

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References

  1. Gabuda SP, Gaidash AA, Kozlova SG, Allan NL (2006) Structural forms of fluorides in bone tissue of animals under chronic fluoride intoxication. J Struc Chem 47(2):258–266

    Article  CAS  Google Scholar 

  2. Water NRC (2006) Fluoride in drinking water: a scientific review of EPA’s standards. EPA

  3. Wang LF, Huang JZ (1995) Outline of control practice of endemic fluorosis in China. Soc Sci Med (1982) 41(8):1191–1195

  4. Watanabe T, Kondo T, Asanuma S, Sakurai S, Tamura K, Ando M (1997) Endemic fluorosis in southern China: radiological findings. Nihon Igaku Hōshasen Gakkai Zasshi Nippon Acta Radiol 57(7):425–426

    CAS  PubMed  Google Scholar 

  5. Wei ZD (2002) Fluoridation in China: a clouded future. Fluoride 35(1):1–4

    CAS  Google Scholar 

  6. Zhang M, Wang A, Xia T, He P (2008) Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-κB in primary cultured rat hippocampal neurons. Toxicol Lett 179(1):1–5

    Article  CAS  PubMed  Google Scholar 

  7. Duan X, Hui X, Ying W, Wang H, Li G, Ling J (2014) Expression of core-binding factor α1 and osteocalcin in fluoride-treated fibroblasts and osteoblasts. J Trace Elem Med Biol 28(3):278–283

    Article  CAS  PubMed  Google Scholar 

  8. Yang T, Zhang Y, Li Y, Hao Y, Zhou M, Dong N, Duan X (2013) High amounts of fluoride induce apoptosis/cell death in matured ameloblast-like LS8 cells by downregulating Bcl-2. Arch Oral Biol 58(9):1165–1173

    Article  CAS  PubMed  Google Scholar 

  9. Song JS, Lee HY, Lee E, Hwang HJ, Kim JH (2002) Cytotoxicity and apoptosis induction of sodium fluoride in human promyelocytic leukemia (HL-60) cells. Environ Toxicol Pharma 11(2):85–91

    Article  CAS  Google Scholar 

  10. Liu YJ, Guan ZZ, Qin G, Pei JJ (2011) Increased level of apoptosis in rat brains and SH-SY5Y cells exposed to excessive fluoride—a mechanism connected with activating JNK phosphorylation. Toxicol Lett 204(s 2–3):183–189

    Article  CAS  PubMed  Google Scholar 

  11. Liu XL, Li CC, Liu KJ, Cui CY, Zhang YZ, Liu Y (2012) The influence of fluoride on the expression of inhibitors of Wnt/β-catenin signaling pathway in rat skin fibroblast cells. Biol Trace Elem Res 148(1):117–121

    Article  CAS  PubMed  Google Scholar 

  12. Cao J, Chen J, Wang J, Jia R, Xue W, Luo Y, Gan X (2013) Effects of fluoride on liver apoptosis and Bcl-2, Bax protein expression in freshwater teleost, Cyprinus carpio. Chemosphere 91(8):1203–1212

    Article  CAS  PubMed  Google Scholar 

  13. Yin S, Song C, Wu H, Chen X, Zhang Y (2015) Adverse effects of high concentrations of fluoride on characteristics of the ovary and mature oocyte of mouse. PLoS One 10(6):133–136

    Google Scholar 

  14. Barbier O, Arreola-Mendoza L, Razo LMD (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2):319–333

    Article  CAS  PubMed  Google Scholar 

  15. Wang S, Bo-ling L, Shao-xian C (2005) The bmd of urine fluoride of children and the study of the relationship between it and activities of akp. Grass-feeding livestock 221–243

  16. Kalisinska E, Bosiacka-Baranowska I, Lanocha N, Kosik-Bogacka D, Krolaczyk K, Wilk A, Kavetska K, Budis H, Gutowska I, Chlubek D (2014) Fluoride concentrations in the pineal gland, brain and bone of goosander (Mergus merganser) and its prey in Odra River estuary in Poland. Environl Geochem Health 36(6):1063–1077

    Article  CAS  Google Scholar 

  17. Irmler IM, Gebhardt P, Hoffmann B, Opfermann T, Figge MT, Saluz HP, Kamradt T (2014) 18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis. Arthritis Res Ther 16(4):155–155

    Article  Google Scholar 

  18. Levy SM, Warren JJ, Phipps K, Letuchy E, Broffitt B, Eichenberger-Gilmore J, Burns TL, Kavand G, Janz KF, Torner JC, Pauley CA (2014) Effects of life-long fluoride intake on bone measures of adolescents: a prospective cohort study. J Dent Res 93(4):353–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Petrone P, Giordano M, Giustino S, Guarino FM (2011) Enduring fluoride health hazard for the Vesuvius area population: the case of AD 79 Herculaneum. PLoS One 6(5):1214–1221

    Google Scholar 

  20. Pera LI, Puche RC, Rigalli A (2007) Potentiometric measurement of ionic, acid-labile and covalently bound fluorine. J Fluor Chem 128(11):1425–1428

    Article  CAS  Google Scholar 

  21. Huang A (2002) Evaluation and analysis on the micro-determination of fluoride in serum and finger blood. J Hygiene Res 31(31):65–66

    CAS  Google Scholar 

  22. Kapoor V, Prasad T, Kapoor V, Prasad T (2001) Blood biochemical constituents in calves following subclinical levels of fluoride toxicosis. Fluoride 34(2):126–131

    CAS  Google Scholar 

  23. Rafique T, Ahmed I, Soomro F, Khan MH, Shirin K (2015) Fluoride levels in urine, blood plasma and serum of people living in an endemic fluorosis area in the Thar Desert, Pakistan. J-Chem Soci Pakistan 37(6):1223–1230

    Google Scholar 

  24. Kumar PS, Aravindakshan CM (2015) Industrial fluorosis and its effects on serum biochemistry and haemogram in cattle of Kerala, India. Proceedings of the National Acad Sci India 85(3):867–872

    Google Scholar 

  25. Palczewska-Komsa M, Kalisińska E, Kosik-Bogacka DI, Lanocha N, Budis H, Baranowska-Bosiacka I, Gutowska I, Chlubek D (2014) Fluoride in the bones of foxes (Vulpes vulpes Linneaus, 1758) and raccoon dogs (Nyctereutes procyonoides Gray, 1834) from north-western Poland. Biol Trace Elem Res 160(1):24–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xiang Q, Chen L, Chen X, Zhang MF (2005) Fluoride and skeletal fluorosis in two villages in Jiangsu Province, China. Fluoride 3838(3):178–184

    Google Scholar 

  27. Fina BL, Lombarte M, Rigalli JP, Rigalli A (2014) Fluoride increases superoxide production and impairs the respiratory chain in ROS 17/2.8 osteoblastic cells. PLoS One 9(6):e100768–e100768

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhi W, Yang X, Yang S, Ren G, Ferreri M, Su Y, Chen L, Han B (2011) Sodium fluoride suppress proliferation and induce apoptosis through decreased insulin-like growth factor-I expression and oxidative stress in primary cultured mouse osteoblasts. Arch Toxicol 85(11):1407–1417

    Article  Google Scholar 

  29. Pereira HA, Leite AL, Charone S, Lobo JG, Cestari TM, Peres-Buzalaf C, Buzalaf MA (2013) Correction: proteomic analysis of liver in rats chronically exposed to fluoride. PLoS One 8(11):8–14

    Article  Google Scholar 

  30. Kobayashi CA, Leite AL, Peresbuzalaf C, Carvalho JG, Whitford GM, Everett ET, Siqueira WL, Buzalaf MA (2014) Bone response to fluoride exposure is influenced by genetics. PLoS One 9(12):e114343–e114343

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tamás L, Huttová J, Mistrík I, Kogan G (2002) Effect of carboxymethyl chitin-glucan on the activity of some hydrolytic enzymes in maize plants. Chem Papers Chemicke Zvesti 56(5):326–329

    Google Scholar 

  32. Chen S, Li B, Shao L, Zhao X, Zhang M, Xia Y, Fang X, Wang J, Hwang SA, Yu S (2013) Change of urinary fluoride and bone metabolism indicators in the endemic fluorosis areas of southern China after supplying low fluoride public water. Bmc Pub Health 13(1):1–10

    Article  Google Scholar 

  33. Jhala DD, Chinoy NJ, Rao MV (2008) Mitigating effects of some antidotes on fluoride and arsenic induced free radical toxicity in mice ovary. Econ Soc 46(3):1138–1142

    CAS  Google Scholar 

  34. Song YE, Tan H, Liu KJ, Liu Y, Lu CR, Yu DL, Tu J, Cui CY (2011) Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP. Environ Health Prev Med 16(3):158–163

    Article  CAS  PubMed  Google Scholar 

  35. Kierdorf U, Kierdorf H, Boyde A (2000) Structure and mineralisation density of antler and pedicle bone in red deer (Cervus elaphus L.) exposed to different levels of environmental fluoride: a quantitative backscattered electron imaging study. J Anat 196(Pt 1) (196):71–83

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research presented here was supported by the MEP-PRC Project 2012ZX07101-002&201509040. The authors are extremely grateful to the staff at the Department of Environment and Health for their technical assistance to the health statistics. The findings and conclusions in this report are those of the authors.

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Authors and Affiliations

  1. Environment and Health Department, Chinese Research Academy of Environmental Sciences, Chaoyang District, Beijing, 100012, China

    Zhou Zhou, Hongmei Wang, Binghui Zheng & Zhang Han

  2. Environment Standard Institute, Chinese Research Academy of Environmental Sciences, Chaoyang District, Beijing, 100012, China

    Yanqing Chen

  3. School of Chemical and Environmental Engineering, China University of Mining and Technology, Beijing, 100083, China

    Yan Ma

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  1. Zhou Zhou
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  2. Hongmei Wang
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  3. Binghui Zheng
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  4. Zhang Han
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  6. Yan Ma
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Corresponding author

Correspondence to Hongmei Wang.

Ethics declarations

All experiments were performed according to the norms of the ethical committee of Jiangsu University (Registration No. SCXK(Su)2009-0002) in accordance with the national guidelines for animal use and care.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Zhou, Z., Wang, H., Zheng, B. et al. A Rat Experimental Study of the Relationship Between Fluoride Exposure and Sensitive Biomarkers. Biol Trace Elem Res 180, 100–109 (2017). https://doi.org/10.1007/s12011-017-0984-4

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  • DOI: https://doi.org/10.1007/s12011-017-0984-4

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