Moderate exercise relieves fluoride-induced liver and kidney inflammatory responses through the IKKβ/NFκB pathway

With the intensification of environmental pollution, the content of fluoride is increasing in human and animal living environments. Long-term fluoride exposure can cause damage to the liver and kidney, which are the main sites for fluoride metabolism, storage and removal. Moreover, exercise often accompanies the entire process of fluoride exposure in humans and animals. However, the mechanism of exercise on fluoride-induced liver and kidney injury remains unclear. Hence, we established a fluoride exposure and/or exercise mouse model to explore the influence of exercise on fluoride-induced liver and kidney inflammation and the potential mechanism. The results showed that fluoride caused obvious structural and functional damage and the notable recruitment of immunocytes in the liver and kidney. In addition, fluoride increased the levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IL-21, TNF-α, and TGF-β but decreased the ratio of IFN-γ/IL-4 and IL-2/IL-10, which indicated that fluoride disturbed the inflammatory balance and caused hepatonephritis. In addition, the expression levels of IKKβ and NFκB were increased, and the expression of IκBα was decreased after fluoride exposure, indicating that fluoride activated the IKKβ/NFκB pathway. In summary, long-term moderate treadmill exercise relieved fluoride-induced liver and kidney inflammatory responses through the IKKβ/NFκB pathway, and exercise can be used to prevent fluoride-induced liver and kidney damage.