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Transcript
The influence of pre and neonatal exposure to sodium fluoride on cyclooxygenases activity in rats
brain
Dec K. [1], Łukomska A. [1], Kolasa A.[3], Tarnowski M.[4], Bociacka-Baranowska I.[2], Chlubek
D.[2], Gutowska I. [1]
1)The Department of Biochemistry and Human Nutrition, Pomeranian Medical University,
Broniewskiego st. 24, 71-460 Szczecin, Poland
2) The Department of Biochemistry, Pomeranian Medical University, Powstańców Wielkopolskich
st. 72, 70-111 Szczecin, Poland
3) The Dapertment of Histology and Embriology, Pomeranian Medical University, Powstańców
Wielkopolskich st. 72, 70-111 Szczecin, Poland
4) d The Dapertment of Physiology, Pomeranian Medical University, Powstańców Wielkopolskich
st. 72, 70-111 Szczecin, Poland
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.