In vivo effects of chronic contamination with depleted uranium on vitamin D3 metabolism in rat
Résumé
The extensive use of depleted uranium (DU) in today's society results in the increase of the number of human population exposed to this radionuclide. The aim of this work was to investigate in vivo the effects of a chronic exposure to DU on vitamin D3 metabolism, a hormone essential in mineral and bone homeostasis. The experiments were carried out in rats after a chronic contamination for 9 months by DU through drinking water at 40 mg/L (1 mg/rat/day). This dose corresponds to the double of highest concentration found naturally in Finland. In DU-exposed rats, the active vitamin D (1,25(OH)2D3) plasma level was significantly decreased. In kidney, a decreased gene expression was observed for cyp24a1, as well as for vdr and rxrα, the principal regulators of CYP24A1. Similarly, mRNA levels of vitamin D target genes ecac1, cabp-d28k and ncx-1, involved in renal calcium transport were decreased in kidney. In the brain lower levels of messengers were observed for cyp27a1 as well as for lxrβ, involved in its regulation. In conclusion, this study showed for the first time that DU affects both the vitamin D active form (1,25(OH)2D3) level and the vitamin D receptor expression, and consequently could modulate the expression of cyp24a1 and vitamin D target genes involved in calcium homeostasis. © 2006 Elsevier B.V. All rights reserved.
Mots clés
calbindin
calcitriol
colecalciferol
cytochrome P450
epithelial calcium channel 1 protein
messenger RNA
protein
sodium calcium exchange protein
uranium
animal experiment
animal model
animal tissue
article
calcium homeostasis
calcium transport
concentration (parameters)
contamination
controlled study
Finland
gene expression
homeostasis
kidney
male
nonhuman
nucleotide sequence
priority journal
protein expression
rat
statistical significance
vitamin D metabolism
Animals
Base Sequence
Cholecalciferol
Cytochrome P-450 CYP27A1
DNA Primers
Drug Contamination
Gene Expression Regulation
Enzymologic
Male
Mitochondria
Liver
Polymerase Chain Reaction
Rats
Sprague-Dawley
Receptors
Calcitriol
Uranium