Biological Trace Element Research

, Volume 180, Issue 1, pp 100–109 | Cite as

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

  • Zhou Zhou
  • Hongmei WangEmail author
  • Binghui Zheng
  • Zhang Han
  • Yanqing Chen
  • Yan Ma


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/(, 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.


Sodium fluoride (NaF) Tissue levels Sensitive biomarkers Enzyme levels 



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.

Compliance with Ethical Standards

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.

Supplementary material

12011_2017_984_MOESM1_ESM.docx (17 kb)
Table S1 (DOCX 16 kb).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Zhou Zhou
    • 1
  • Hongmei Wang
    • 1
    Email author
  • Binghui Zheng
    • 1
  • Zhang Han
    • 1
  • Yanqing Chen
    • 2
  • Yan Ma
    • 3
  1. 1.Environment and Health DepartmentChinese Research Academy of Environmental SciencesBeijingChina
  2. 2.Environment Standard InstituteChinese Research Academy of Environmental SciencesBeijingChina
  3. 3.School of Chemical and Environmental EngineeringChina University of Mining and TechnologyBeijingChina

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