Biological Trace Element Research

, Volume 172, Issue 1, pp 172–178 | Cite as

Changes in Liver Antioxidant Status of Offspring Mice Induced by Maternal Fluoride Exposure During Gestation and Lactation

  • Ruiyan Niu
  • Haijun Han
  • Yuliang Zhang
  • Jinming Wang
  • Jianhai Zhang
  • Wei Yin
  • Xiufang Yin
  • Zilong SunEmail author
  • Jundong WangEmail author


Excessive fluoride intake for a long time has been demonstrated to provoke hepatic oxidative stress in adults. However, the response to fluoride toxicity of liver in newborns exposed to fluoride during embryonic and suckling stages remains unclear. In this study, female Kunming mice were administrated with 25, 50, and 100 mg/L sodium fluoride (NaF) from prenatal day 0 to day 21 after delivery, and the antioxidative status in the liver of their pups at postnatal day 21 was evaluated. The results showed that compared with the control group, NaF significantly increased malondialdehyde (MDA) level and reduced catalase (CAT) activity, while no statistical difference was observed in activities and mRNA expressions of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Notably, with comparison to the controls, the protein level of CAT was significantly reduced in medium- and high-fluoride groups, while its relative mRNA abundance was enhanced which could result from the encouragement of the lowered CAT protein expression. These findings suggested that CAT was more susceptible to low-fluoride exposure in early life.


Fluoride Gestation and lactation Liver Mice Offspring 



This study was supported by the China National Natural Science Foundation (Grant Nos. 31201965, 31101869, and 31172376), Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi, and Program for the Top Young Innovative Talents of Shanxi Agricultural University (Grant No. TYIT201407).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


  1. 1.
    Doull J, Boekelheide K, Farishian BG et al (2006) Fluoride in drinking water: a scientific review of EPA’s standards. National Academies Press, WashingtonGoogle Scholar
  2. 2.
    Finkelman RB, Belkin HE, Zheng B (1999) Health impacts of domestic coal use in China. Proc Natl Acad Sci U S A 96(7):3427–3431CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rohlom K (1937) Fluorine intoxication: a clinical hygienic study with a review of the literature and some experimental investigations. HK Lewis, LondonGoogle Scholar
  4. 4.
    Prystupa J (2011) Fluorine--a current literature review. An NRC and ATSDR based review of safety standards for exposure to fluorine and fluorides. Toxicol Mech Methods 21(2):103–170CrossRefPubMedGoogle Scholar
  5. 5.
    Wang JD, Hong JH, Li JP et al (2002) Effect of high fluoride and low protein on tooth matrix development in goats. Fluoride 35(1):51–55Google Scholar
  6. 6.
    Bouaziza H, Ketatab S, Jammoussic K et al (2006) Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups. Pestic Biochem Phys 86(3):124–130CrossRefGoogle Scholar
  7. 7.
    Hassan HA, Yousef MI (2009) Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced hepatotoxicity and oxidative stress in rats. Food Chem Toxicol 47(9):2332–2337CrossRefPubMedGoogle Scholar
  8. 8.
    Thangapandiyan S, Miltonprabu S (2013) Epigallocatechin gallate effectively ameliorates fluoride-induced oxidative stress and DNA damage in the liver of rats. Can J Physiol Pharmacol 91(7):528–537CrossRefPubMedGoogle Scholar
  9. 9.
    Perumal E, Paul V, Govindarajan V et al (2013) A brief review on experimental fluorosis. Toxicol Lett 223(2):236–251CrossRefPubMedGoogle Scholar
  10. 10.
    Opydo-Szymaczek J, Borysewicz-Lewicka M (2007) Transplacental passage of fluoride in pregnant Polish women assessed on the basis of fluoride concentrations in maternal and cord blood plasma. Fluoride 40(1):46–50Google Scholar
  11. 11.
    Shimonovitz S, Patz D, Ever-Hadani P et al (1995) Umbilical cord fluoride serum levels may not reflect fetal fluoride status. J Perinat Med 23(4):279–282CrossRefPubMedGoogle Scholar
  12. 12.
    Montherrat-Carret L, Perrat-Mabilon B, Barbey E et al (1996) Chemical and X-Ray analysis of fluoride, phosphorus and calcium in human foetal blood and hard tissues. Arch Oral Biol 41(12):1169–1178CrossRefPubMedGoogle Scholar
  13. 13.
    Faraji H, Mohammadi AA, Akbari-Adergani B et al (2014) Correlation between fluoride in drinking water and its levels in breast milk in Golestan Province, Northern Iran. Iran J Public Health 43(12):1664–1668PubMedPubMedCentralGoogle Scholar
  14. 14.
    Gupta P, Gupta N, Meena K et al (2015) Concentration of fluoride in cow’s and buffalo’s milk in relation to varying levels of fluoride concentration in drinking water of Mathura City in India- a pilot study. J Clin Diagn Res 9(5):LC05–LC07PubMedPubMedCentralGoogle Scholar
  15. 15.
    Gordillo M, Evans T, Gouon-Evans V (2015) Orchestrating liver development. Development 142(12):2094–2108CrossRefPubMedGoogle Scholar
  16. 16.
    Kanagaraj VV, Panneerselvam L, Govindarajan V et al (2015) Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: a possible mechanism. Biofactors 41(2):90–100CrossRefPubMedGoogle Scholar
  17. 17.
    Song GH, Huang FB, Gao JP et al (2015) Effects of fluoride on DNA damage and caspase-mediated apoptosis in the liver of rats. Biol Trace Elem Res 166(2):173–182CrossRefPubMedGoogle Scholar
  18. 18.
    Shanthakumari D, Srinivasalu S, Subramanian S (2004) Effect of fluoride intoxication on lipidperoxidation and antioxidant status in experimental rats. Toxicology 204(2-3):219–228CrossRefPubMedGoogle Scholar
  19. 19.
    Zorn AM (2008) Liver development. Stembook, Harvard Stem Cell Institute, CambridgeGoogle Scholar
  20. 20.
    Blaszczyk I, Birkner E, Kasperczyk S (2011) Influence of methionine on toxicity of fluoride in the liver of rats. Biol Trace Elem Res 139(3):325–331CrossRefPubMedGoogle Scholar
  21. 21.
    Wang YN, Xiao KQ, Liu JL et al (2000) Effect of long term fluoride exposure on lipid composition in rat liver. Toxicology 146(2-3):161–169CrossRefPubMedGoogle Scholar
  22. 22.
    Jackson R, Kelly S, Noblitt T et al (1994) The effect of fluoride therapy on blood chemistry parameters in osteoporotic females. Bone Miner 27(1):13–23CrossRefPubMedGoogle Scholar
  23. 23.
    Chlubek D (2003) Fluoride and oxidative stress. Fluoride 36(4):217–228Google Scholar
  24. 24.
    Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2):319–333CrossRefPubMedGoogle Scholar
  25. 25.
    Bharti VK, Srivastava RS, Kumar H et al (2014) Effects of melatonin and epiphyseal proteins on fluoride-induced adverse changes in antioxidant status of heart, liver, and kidney of rats. Adv Pharmacol Sci 2014:532969PubMedPubMedCentralGoogle Scholar
  26. 26.
    Agalakova NI, Gusev GP (2012) Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biol 2012:403835CrossRefGoogle Scholar
  27. 27.
    Shivarajashankara YM, Shivashankara AR, Hanumanth Rao S et al (2001) Oxidative stress in children with endemic skeletal fluorosis. Fluoride 34(2):103–107Google Scholar
  28. 28.
    Kalyanalakshmi P, Vijayabhaskar M, Dhananjaya Naidu M (2007) Lipid peroxidation and antioxidant enzyme status of adult males with skeletal fluorosis in Andhra Pradesh, India. Fluoride 40(1):42–45Google Scholar
  29. 29.
    Mukhopadhyay D, Chattopadhyay A (2014) Induction of oxidative stress and related transcriptional effects of sodium fluoride in female zebrafish liver. Bull Environ Contam Toxicol 93(1):64–70CrossRefPubMedGoogle Scholar
  30. 30.
    Jin Y, Zhang X, Shu L et al (2010) Oxidative stress response and gene expression with atrazine exposure in adult female zebrafish (Danio rerio). Chemosphere 78(7):846–852CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ruiyan Niu
    • 1
    • 2
  • Haijun Han
    • 1
    • 3
  • Yuliang Zhang
    • 1
  • Jinming Wang
    • 1
    • 2
  • Jianhai Zhang
    • 1
    • 2
  • Wei Yin
    • 1
  • Xiufang Yin
    • 4
  • Zilong Sun
    • 1
    • 2
    Email author
  • Jundong Wang
    • 1
    • 2
    Email author
  1. 1.College of Animal Science and TechnologyShanxi Agricultural UniversityTaiguChina
  2. 2.Shanxi Key Laboratory of Environmental Veterinary MedicineShanxi Agricultural UniversityTaiguChina
  3. 3.School of MedicineZhejiang UniversityHangzhouChina
  4. 4.Yanli Animal Husbandry and Veterinary StationJinchengChina

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