In vivo effects of chronic contamination with depleted uranium on vitamin D3 metabolism in rat

  • La recherche

  • Recherche

01/02/2007

Titre de la revue : Biochimica et Biophysica Acta. General Subjects
Volume : 1770
N° : 2
Pagination : 266-272
Date de publication : 01/02/2007
Type de document > *Article de revue
Mots clés publication scientifique > contamination chronique , cytochrome P 450 , récepteur vitamine D , uranium appauvri , vitamine D3
Unité de recherche > IRSN/DRPH/SRBE/LRTOX
Auteurs > AIGUEPERSE Jocelyne , GOURMELON Patrick , GRANDCOLAS Line , GUEGUEN Yann , LOBACCARO Jean-Marc , SOUIDI Maâmar , TISSANDIE Emilie , VOISIN Philippe

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 lxrß, 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.

En savoir plus
Texte complet
Contact