Adaptive responses of the ileum of NOD mice to low-dose fluoride: A proteomic exploratory study.

Fluoride (F) has been employed worldwide to control dental caries. More recently, it has been suggested that the consumption of low doses of F in the drinking water may reduce blood glucose levels, introducing a new perspective for the use of F for the management of blood glucose. However, the exact mechanism by which F affects blood glucose levels remains largely unexplored. Given that the small gut plays a pivotal role in glucose homeostasis, the aim of this study was to investigate the proteomic changes induced by low doses of F in the ileum of female nonobese-diabetic (NOD) mice. Forty-two female NOD mice were divided into two groups based on the F concentration in their drinking water for 14 weeks: 0 (control) or 10 mgF/L. At the end of the experimental period, the ileum was collected for proteomic and Western blot analyses. Proteomic analysis indicated an increase in isoforms of actin, gastrotropin, several H2B histones, and enzymes involved in antioxidant processes, as well as a decrease in enzymes essential for energy metabolism. In summary, our data indicates an adaptive response of organism to preserve protein synthesis in the ileum, despite significant alterations in energy metabolism typically induced by F, therefore highlighting the safety of controlled fluoridation in water supplies.

Effect of Physical Exercise and Genetic Background on Glucose Homeostasis and Liver/Muscle Proteomes in Mice.

We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice. In R-mice, exercise resulted in an increase in F accumulation in the femur. In S-mice, the mean plasma glucose level was significantly higher in Group II compared with Groups I and III. There was an increase in liver proteins involved in energy flux and antioxidant enzymes in non-exercise groups (I, II) of S-mice in comparison with the corresponding groups of R-mice. The results also showed a decrease in muscle protein expression in Group I S-mice compared with their R-mice counterparts. In conclusion, the findings suggest an increased state of oxidative stress in fluorosis-susceptible mice that might be exacerbated by the treatment with F. In addition, fluorosis-susceptible mice have plasma glucose levels higher than fluorosis-resistant mice on exposure to F, and this is not affected by exercise.