Abstract: The fluoride widely present in water and food of livestock and poultry seriously threatens the liver health of livestock and poultry and the safety of animal food. To elucidate the internal mechanism of fluoride-induced liver injury, and clarify the regulatory role of IL-17A in fluoride-induced liver inflammation and hepatocyte apoptosis, this study randomly divided 24 wild-type C57 mice and 12 IL-17A knockout mice into control, NaF, and KO+NaF groups. In addition, HE staining, ELISA, flow cytometry, and immunohistochemistry were used to detect the changes of morphology, inflammatory cells, inflammatory factors, and apoptosis in the liver. The results showed that fluoride exposure induced liver morphology damage, increased the content of inflammatory factors (TNF-α, IL-17A, INF-γ, IL-23, TGF-β) and the levels of M2 macrophages and dendritic cells, decreased the levels of IL-1β, natural killer cells, γδT cells, CD4⁺T cells and the ratio of CD4⁺T cells/CD8⁺T cells in the liver. In addition, the results of apoptosis detection showed that fluoride exposure increased the apoptotic cells and the protein expression levels of key apoptosis genes Cyt-c and Caspase3 in the liver. However, compared with the NaF group, the liver injury was alleviated, the contents of inflammatory factors (INF-γ, TNF-α, TGF-β, IL-23, IL-17A) and dendritic cells were significantly reduced, and the number of apoptotic cells and the protein expression levels of Cyt-c and Caspase3 were significantly decreased in the liver of KO+NaF group. In summary, IL-17A knockout alleviated fluoride-induced inflammatory response and hepatocyte apoptosis. This study provides theoretical basis and new ideas for the research and the scientific prevention/treatment of fluorotoxic liver injury.

Key words: fluorosis, IL-17A, liver, inflammatory response, apoptosis