Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues

Abstract

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

Nitrate and Phosphate Transporters Rescue Fluoride Toxicity in Yeast

“…These observations suggest that fluoride inhibits the transport of nutrients. Several previous reports found that fluoride can inhibit glucose import. − We tested for Pho87p/Pho90p inhibition by monitoring phosphate uptake under increasing fluoride (Figure A). Simultaneous addition of fluoride with phosphate showed no detectable difference in phosphate uptake.…”

Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health

“…A significant effect of F on OC expression has been found to occur in adults at serum F levels of 1.0 μM [154] or when urinary F levels exceed 0.62 mg/L in adolescent children [155]. Consistent with this data, several in-vivo studies have reported that chronic F exposure enhances plasma insulin levels and promotes insulin resistance in rodents [211,212,213,214,215]. A similar association has also been found in humans chronically exposed to F [216].…”

Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours—A Research Hypothesis

“…Fluoride exposure may be associated with changes in the profile of proteins involved in energy metabolism [ 64 ], and researchers have suggested that impaired glucose metabolism in neurons is correlated with decreased expression of the GLUT-1 transporter [ 65 ]. On the other hand, increased glucose transport into brain cells has also been documented, although without changes in transporter expression, suggesting a compensatory mechanism in response to damage [ 66 ]. Chronic fluoride exposure also affects amino acid and lipid metabolism [ 61 , 67 ].…”

“…Studies in rats have shown that NaF decreases the expression of GLUT1, a glucose transporter in the brain, but the results of the few existing studies are conflicting. Some point to decreased expression of the GLUT1 glucose transporter and reduced glucose uptake into the brain [ 65 ], while others report compensatory increases in glucose uptake in the brain and peripheral tissues without significant changes in GLUT1 and GLUT3 expression [ 66 ]. Due to the paucity of data on the molecular mechanism underlying the effects of fluoride on brain glucose uptake, transport, and metabolism, it is difficult to clearly assess its role in glioma progression and invasiveness.…”