Metabolic effect of low levels of fluoride in the islets of NOD mice

Introduction: Fluoride (F) has been largely employed for the control of dental caries, in addition to studies suggesting beneficial effects against diabetes when a low dose of F is added in the drinking water (10 mgF/L). Objectives: This study evaluated metabolic changes in the pancreatic islets of NOD mice exposed to low dose of F and the main pathways altered by the treatment. Methodology: Forty-two female NOD mice were randomly divided into two groups, taking into account the F concentration administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results: In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon and acetylated histone H3, despite the treated group had higher percentages than the control. In addition, no significant differences were found for the average percentages of pancreatic areas occupied by islets and the pancreatic inflammatory infiltrate between the control and treated groups. For proteomic analysis we found great increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data indicates an attempt of the organism to maintain protein synthesis in the islets, even upon the dramatic changes in energy metabolism. Conclusion: Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in the water from the public supply consumed by humans.