Self-recovery study of the adverse effects of fluoride on small intestine: Involvement of pyroptosis induced inflammation

Abstract Increasing investigations suggest that fluoride (F) exposure was associated with gastrointestinal diseases, but related literatures were still largely insufficient and the underlying mechanisms have not been fully elucidated. Moreover, previous study in our lab reported F toxicity has the reversible tendency, but it still needs to be further explored. To address this issue, we established a 90 days F exposure and 15 days & 30 days self-recovery mice model, including control and three F groups (25, 50 and 100 mg/L sodium fluoride (NaF)) in each period. The results revealed that after 90 days F exposure, histological structure and ultrastructure of small intestine were markedly disrupted; the value of villus height to crypt depth, and expressions of tight junctions related mRNA and proteins were significantly decreased; intestinal permeability, pro-inflammatory cytokines and pyroptosis related mRNA and proteins were notably increased in duodenum, jejunum and ileum. However, intriguingly, after 30 days recovery period, indices in F groups almost all have recovered towards normalcy. Collectively, this study demonstrated that F exposure could impair the structure and epithelial barrier function of small intestine, leading to the intestinal inflammation, and pyroptosis may contribute to this damage; Furthermore, F toxicity on small intestine is reversible, and could be restored when off the F exposure environment for a certain period of time. Additionally, among the three regions of small intestine, duodenum seems more vulnerable to F exposure than jejunum and ileum.