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Th17-Related Cytokines Involved in Fluoride-Induced Cecal and Rectal Barrier Damage of Ovariectomized Rats

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Abstract

To investigate fluoride (F)-induced intestine barrier damage and the role of estrogen deficiency in this progress, a rat model of estrogen deficiency was established through bilateral surgical removal of ovaries. The F exposure model was then continued by adding sodium fluoride (0, 25, 50, and 100 mg/L, calculated on a fluorine ion basis) to drinking water for 90 days. Afterward, intestinal mucosal structure, barrier function, and inflammatory cytokines were evaluated. The results showed that excessive F decreased the developmental parameters (crypt depth) of the cecum and rectum and inhibited the proliferation capacity of the intestinal epithelia, which are more obvious in the state of estrogen deficiency. The distribution of goblet cells and glycoproteins in the intestinal mucosa decreased with the increase in F concentration, and estrogen deficiency led to a further decline, especially in the rectum. Using the immunofluorescence method, the study showed that excessive F caused interleukin-17A (IL-17A) significantly decrease in the cecum and increase in the rectum. Meanwhile, F treatment remarkably upregulated the expression of intestinal IL-1β, IL-23, and IL-22, while the level of IL-6 was downregulated. In addition, estrogen deficiency increased IL-1β, IL-6, IL-23, and IL-22, but decreased IL-17A expression in the cecum and rectum. Collectively, F exposure damaged intestinal morphological structure, inhibited epithelial cell proliferation and mucus barrier function, and resulted in the disturbance of T helper (Th) 17 cell-related cytokines expression. Estrogen deficiency may further aggravate F-induced damage to the cecum and rectum.

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Funding

This work was supported by the National Natural Science Foundation of China (grant no.·32102740) and the Natural Science Foundation of Henan, China (Grant no. 202300410120).

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Authors and Affiliations

  1. Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, 471000, Henan, People’s Republic of China

    Xiao-ying Gao, Ye Jin, Jing Zhao, Yu-ling Zhang, Hong-wei Wang & Bian-hua Zhou

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  1. Xiao-ying Gao
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  2. Ye Jin
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  3. Jing Zhao
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  4. Yu-ling Zhang
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Contributions

Xiao-ying Gao: formal analysis, writing the original draft, and preparation of the data presentation. Ye Jin: visualization, validation, and data curation. Jing Zhao: funding acquisition and validation. Yu-ling Zhang: validation and project administration. Hong-wei Wang: ideas, investigation, and critical review. Bian-hua Zhou: funding acquisition and validation, conceptualization, methodology, review and editing, and provision of resources.

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Correspondence to Bian-hua Zhou.

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Gao, Xy., Jin, Y., Zhao, J. et al. Th17-Related Cytokines Involved in Fluoride-Induced Cecal and Rectal Barrier Damage of Ovariectomized Rats. Biol Trace Elem Res 201, 4497–4507 (2023). https://doi.org/10.1007/s12011-022-03519-6

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