Genetics and environmental influences on fluoride metabolism and retention

Abstract

Fluoride (F) is extremely important for public health due to its properties to prevent or reverse caries in individuals of all ages. It can pose risks if consumed or applied indiscriminately or inappropriately. The main side effect of excessive use of fluoride is dental fluorosis. After absorption, F enters the blood stream and is distributed to the whole organism. It is stored mainly in calcified tissues. Its excretion occurs essentially via the kidney. Several molecular mechanisms involving F metabolism are still unknown. In the last decade, many studies have reported the influence of genetic factors in the susceptibility to dental fluorosis. Interesting studies employed mouse strains that have very different responses to the effects F. Thus, there is evidence that resistance or susceptibility to fluorosis seem to be influenced by genetic factors as well as by the interaction with the environment, such as physical activity. The aim of the present proposal is, through proteomics analysis, to identify proteins that are altered in kidney, liver, muscle and intestine of mice susceptible or resistant to fluorosis in response to changes in exposure F, with and without physical exercise. Therefore, 90 mice of A/J (n = 45) and 129P J (n = 45) strains, susceptible and resistant to fluorosis, respectively, will be obtained. The animals from each strain will be divided into 3 groups, according to the treatment (n=15/group), as follows: a) no exposure to F, no physical exercise; b) drinking water containing 50 ppm F (as NaF) for 56 days and no physical exercise; c) drinking water containing 50 ppm F (as NaF) for 56 days plus physical exercise (daily running for 5 days/week on a treadmill for 60 minutes at high intensity). After the experimental period, the animals will be submitted to euthanasia for samples collection and analysis. F will be analyzed in plasma, liver, kidney and femur. Liver, kidney, muscle and intestine will be submitted to shotgun proteomic analysis. Plasma glucose and insulin levels will be also evaluated. After being checked for normality and homogeneity, data will be submitted to appropriate statistic tests (p<0.05). (AU)