Long-term exposure to fluoride as a factor promoting changes in the expression and activity of cyclooxygenases (COX1 and COX2) in various rat brain structures.
Animals
Animals, Newborn
Brain
/ drug effects
Cyclooxygenase 1
/ biosynthesis
Cyclooxygenase 2
/ biosynthesis
Dinoprostone
/ biosynthesis
Female
Fluorides
/ pharmacokinetics
Gene Expression Regulation, Enzymologic
/ drug effects
Membrane Proteins
/ biosynthesis
Neurotoxicity Syndromes
/ enzymology
Pregnancy
Prenatal Exposure Delayed Effects
/ enzymology
Prostaglandins
/ biosynthesis
Rats
Rats, Wistar
Thromboxane B2
/ biosynthesis
Brain
Cyclooxygenase
Fluoride
Inflammation
Neurotoxicity
Journal
Neurotoxicology
ISSN: 1872-9711
Titre abrégé: Neurotoxicology
Pays: Netherlands
ID NLM: 7905589
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
28
01
2019
revised:
03
06
2019
accepted:
03
06
2019
pubmed:
9
6
2019
medline:
19
5
2020
entrez:
9
6
2019
Statut:
ppublish
Résumé
Sixty percent of the mammalian brain is composed of lipids including arachidonic acid (AA). AA released from cell membranes is metabolised in the cyclooxygenase (COX) pathway to prostanoids - biologically active substances involved in the regulation of many processes including inflammation. It has been shown that long-term exposure to fluoride in pre and neonatal period is dangerous because this element is able to penetrate through the placenta and to cross the blood-brain barrier. Exposure to fluoride during the development affects metabolism and physiology of neurons and glia which results in the impairment of cognitive functions but the exact mechanisms of fluoride neurotoxicity are not clearly defined. The aim of this study was to determine whether exposure to fluoride during the development affects COXes activity and the synthesis of prostanoids. Pre- and postnatal toxicity model in Wistar rats was used. Experimental animals received 50 mg/L of NaF in drinking water ad libitum, while control animals received tap water. In cerebral cortex, hippocampus, cerebellum and striatum were measured fluoride concentration, COX1 and COX2 genes expression, immunolocalization of the enzymatic proteins and concentration of PGE2 and TXB2. of this study showed statistically significant changes in the concentration of fluoride in brain structures between study group and control animals. Moreover, significant changes in the expression level of COX1 and COX2, and in the concentration of PGE2 and TXB2 were observed. Exposure to fluoride in the prenatal and neonatal period result in the increase in COX2 activity and increase in PGE2 concentration in rats brain, which may lead to disturbances in central nervous system homeostasis..
Sections du résumé
BACKGROUND
Sixty percent of the mammalian brain is composed of lipids including arachidonic acid (AA). AA released from cell membranes is metabolised in the cyclooxygenase (COX) pathway to prostanoids - biologically active substances involved in the regulation of many processes including inflammation. It has been shown that long-term exposure to fluoride in pre and neonatal period is dangerous because this element is able to penetrate through the placenta and to cross the blood-brain barrier. Exposure to fluoride during the development affects metabolism and physiology of neurons and glia which results in the impairment of cognitive functions but the exact mechanisms of fluoride neurotoxicity are not clearly defined.
OBJECTIVE
The aim of this study was to determine whether exposure to fluoride during the development affects COXes activity and the synthesis of prostanoids.
MATERIAL AND METHODS
Pre- and postnatal toxicity model in Wistar rats was used. Experimental animals received 50 mg/L of NaF in drinking water ad libitum, while control animals received tap water. In cerebral cortex, hippocampus, cerebellum and striatum were measured fluoride concentration, COX1 and COX2 genes expression, immunolocalization of the enzymatic proteins and concentration of PGE2 and TXB2.
RESULTS
of this study showed statistically significant changes in the concentration of fluoride in brain structures between study group and control animals. Moreover, significant changes in the expression level of COX1 and COX2, and in the concentration of PGE2 and TXB2 were observed.
CONCLUSION
Exposure to fluoride in the prenatal and neonatal period result in the increase in COX2 activity and increase in PGE2 concentration in rats brain, which may lead to disturbances in central nervous system homeostasis..
Identifiants
pubmed: 31175943
pii: S0161-813X(19)30051-8
doi: 10.1016/j.neuro.2019.06.001
pii:
doi:
Substances chimiques
Membrane Proteins
0
Prostaglandins
0
Thromboxane B2
54397-85-2
Cyclooxygenase 1
EC 1.14.99.1
Cyclooxygenase 2
EC 1.14.99.1
Ptgs1 protein, rat
EC 1.14.99.1
Ptgs2 protein, rat
EC 1.14.99.1
Dinoprostone
K7Q1JQR04M
Fluorides
Q80VPU408O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-90Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.