Effects of Excess Fluoride and Iodide on Thyroid Function and Morphology
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Abstract
Exposure to high levels of iodide in Cangzhou, Shandong Province, China has been associated with increased incidence of thyroid disease; however, whether fluoride can affect the thyroid remains controversial. To investigate the effects of excess fluoride, we evaluated thyroid gland structure and function in rats exposed to fluoride and iodide, either alone or in combination. Five-week-old Wistar rats (n = 160 total) were randomly divided into eight groups: three groups that were given excess fluoride (15, 30, or 60 ppm F); one group given excess iodide (1200 μg/L I); three groups given excess iodide plus fluoride (1200 μg/L I plus 15, 30, or 60 ppm F); and one control group. The serum concentrations of the thyroid hormones TT3 and TT4 on day 150 were significantly reduced for certain fluoride groups; however, no significant differences were observed in concentrations for the pituitary hormone TSH among any groups. Hematoxylin and eosin staining revealed that iodide causes an increase in the areas of the colloid lumens and a decrease in the diameters of epithelial cells and nuclei; however, fluoride causes an increase in nuclear diameters. The damage to follicular epithelial cells upon fluoride or iodide treatment was easily observed by transmission electron microscopy, but the effects were most dramatic upon treatment with both fluoride and iodide. These results suggest that iodide causes the most damage but that fluoride can promote specific changes in the function and morphology of the thyroid, either alone or in combination with iodide.
Keywords
Fluoride excess Iodide excess Thyroid Function MorphologyNotes
Acknowledgments
The authors thank Chenling Fan and Hong Wang for the excellent technical assistance. They would also like to thank all colleagues and students who contributed to this study. It would not have been possible without their help. The research was supported by Dr. Weiping Teng’s scientific research funds.
Conflict of Interest
All authors declare there is no actual or potential interest with other people or organizations within the 3 years of beginning this work.
References
- 1.Ares S, Quero J, Morreale G (2008) Iodine balance, iatrogenic excess and thyroid dysfunction in premature newborns. Semin Perinatol 32:407–412CrossRefPubMedGoogle Scholar
- 2.Wu Y, Li X, Chang S, Liu L, Zou S, Hipgrave DB (2012) Variable iodide intake persists in the context of universial salt iodization in China. J Nutr 142:1728–1734PubMedPubMedCentralGoogle Scholar
- 3.Du Y, Gao Y, Meng F, Liu S, Fan Z, Wu J, Sun D (2014) Iodine deficiency and excess coexist in China and induce thyroid dysfunction and disease: a cross-sectional study. PLoS One 6:9Google Scholar
- 4.Meng F, Zhao R, Liu P, Liu L, Liu S (2013) Assessment of iodine status in children, adults, pregnant women and lactating women in iodine-replete areas of China. PLoS One 25:8Google Scholar
- 5.Guan H, Shan Z, Teng X, Li Y, Teng D, Jin Y, Yu X, Fan C, Chong W, Yang F, Dai H, Yu Y, Li J, Chen Y, Zhao D, Shi X, Hu F, Mao J, Gu X, Yang R, Chen W, Tong Y, Wang W, Gao T, Li C, Teng W (2008) Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes. Clin Endocrinol 69:136–141CrossRefGoogle Scholar
- 6.Wang H, Yang Z, Zhou B, Gao H, Yan X, Wang J (2009) Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level. Toxicol Ind Health 25:49–57CrossRefPubMedGoogle Scholar
- 7.Kutlucan A, Kale Koroglu B, Numan Tamer M (2013) The investigation of effects of fluorosis on thyroid volume in school-age children. Med Glas (Zenica) 10:93–98Google Scholar
- 8.Zeng Q, Cui YS (2012) Studies of fluoride on the thyroid cell apoptosis and mechanism. Zhonghua Yu Fang Yi Xue Za Zhi 46:233–236PubMedGoogle Scholar
- 9.Liu GY (2012) Role of nitric oxide and vascular endothelial growth factor in fluoride-induced goitrogenesis in rats. Environ Toxicol Pharmacol 34:209–217CrossRefPubMedGoogle Scholar
- 10.Basha PM, Rai P, Begum SF (2011) Fluoride toxicity and status of serum thyroid hormones, brain histopathology, and learning memory in rats: a multigenerational assessment. Biol Trace Elem Res 144:1083–1094CrossRefPubMedGoogle Scholar
- 11.Zhao HF, Chai LH, Wang HY (2013) Effects of fluoride on metamorphosis, thyroid and skeletal development in Bufo gargarizanstadpoles. Ecotoxicology 22:1123–1132CrossRefPubMedGoogle Scholar
- 12.Jenq SF, Jap TS, Hsieh MS, Chiang H (1993) The characterization of adenyl cyclase activity in FRTL-5 cell line. Chinese Medical Journal (Taipei) 51:159–165Google Scholar
- 13.Miller GM (1993) The effect of fluoride on high plants. Fluoride 26:3–22Google Scholar
- 14.Banji D (2013) Investigation on the role of Spirulina platensisin ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride. Food Chem 140:321–331CrossRefPubMedGoogle Scholar
- 15.Shin R, Uehiya M, Bartlett JD (2008) Fluoride induces endoplasmic reticulum stress and inhibits protein synthesis and secretion. Environ Health Perspect 116:l142–l146CrossRefGoogle Scholar
- 16.Vitale M, Di Matola T, D’Ascoli F, Salzano S, Bogazzi F, Fenzi G, Martino E, Rossi G (2000) Iodide excess induces apoptosis in thyroid cells through a P53-independent mechanism involving oxidative stress. Endocrinology 141:598–604PubMedGoogle Scholar
- 17.Carayanniotis G (2011) Molecular parameters linking thyroglobulin iodination with autoimmune thyroiditis. Hormones (Athens) 10:27–35CrossRefGoogle Scholar
- 18.Teng X, Shan Z, Teng W, Fan C, Wang H, Guo R (2009) Experimental study on the effects of chronic iodine excess on thyroid function, structure, and autoimmunity in autoimmune-prone NOD.H-2h4 mice. Clin Exp Med 9: 51–59Google Scholar
- 19.Liu HL, Zeng Q (2014) The role of the IRE1 pathway in excessive iodide- and/or fluoride-induced apoptosis in Nthy-ori 3-1 cells in vitro.Toxicology Letters l224: 341–348Google Scholar
- 20.Liu H, Zeng Q, Cui Y, Yu L, Zhao L, Hou C, Zhang S, Zhang L, Fu G, Liu Y, Jiang C, Chen X, Wang A (2014) The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity. Environ Toxicol Pharmacol 38:332–340CrossRefPubMedGoogle Scholar