Title : The influence of pre and neonatal exposure to sodium fluoride on cyclooxygenases activity in rats brain
Long term exposure to fluorine in pre and neonatal period is dangerous because this element is able to penetrate through the placenta and to cross the blood-brain barrier. Young individuals are less resistant to the toxic influence of fluorine due to the fact that their defensive mechanisms are not fully developed and the permeability of the blood-brain barrier is higher than among adults. Prolonged exposure to fluorine during the development affects metabolism and physiology of neurons and glia which results in the impairment of cognitive functions. Epidemiological studies have shown that children who live in geographical regions in which drinking water is contaminated with fluoride, have a statistically significant decreased level of intelligence in comparison to children from regions not contaminated with this element. The exact mechanisms by which fluorine influence cognitive functions and decreases learning abilities are not clearly defined. Changes in central nervous system functioning after fluorine exposure have been studied in terms of its influence on the synthesis of neurotransmitters and proinflammatory factors, initiation of oxidative stress and the apoptosis of cells.The aim of this study was to determine whether exposure to fluorine during the development affects cyclooxygenases activity and the synthesis of prostanoids.
Toxicity model in vivo in male and female Wistar rats was used. Pregnant experimental females received 50 mg/L of sodium fluoride (NaF) in drinking water ad libitum since the first day of pregnancy till the labour and during breast-feeding. Offsprings were being fed by their mothers till 4th week (21st day of their life). After that they have been weaned and they received drinking water with sodium fluoride until the end of 3rd month. Control animals received tap water. Animals were killed and organs were removed including brain. In different brain structures (cerebral cortex, hippocampus, cerebellum and striatum) were measured fluoride concentration, cyclooxyganse-1 (COX-1) and cyclooxygenase-2 (COX-2) genes expression, immunolocalization of the enzymatic proteins and concentration of PGE2 and TXB2. Potentiometry, RT-PCR, immunohistochemistry and immunoenzimatic methods were used to receive the results.
Results of this study showed statistically significant changes in the concentration of fluorine in different brain structures between experimental group and control animals. Moreover.significant changes in the expression level of COX-1 and COX-2, and in the concentration of PGE2 and TXB2 were obsered after pre and neonatal exposure to sodium fluoride.
Fluorine is able to cross blood-brain barrier and accumulate in central nervous system (CNS). Pre- and neonatal exposure to this element affects COX-genes expression. Prostanoids such as PGE2 and TXB2 - products of COX activity, under normal conditions control some brain functions but changes in their concentrations can initiate inflammation and disturb homeostasis of CNS. Exposure to fluorine during the development affects neurons metabolism by changes in prostanoids synthesis.