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Effects of depleted uranium after short-term exposure on vitamin D3 metabolism in rat
Publication CNRS
Auteur(s):TISSANDIE (E.),  GUEGUEN (Y.),  LOBACCARO (J. M. A.),  PAQUET (F.),  AIGUEPERSE (J.),  SOUIDI (M.), 
Affiliation(s):Radiological Protection and Human health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, Institute for Radiological protection and Nuclear Safety, BP n 17, 92262 Fontenay-aux-Roses, France;
Compared Physiology and Molecular Endocrinology, UMR Université Blaise Pascal-CNRS, 24 avenue des Landais, 6547, 63177 Aubière, France;
Source:Archives of toxicology; vol. 80; no. 8; pp. 473-480;
Pays de publication:Allemagne;
Date de publication: 2006
ISSN:0340-5761
Langue du document:Anglais
Notes:43 ref.;

Type de document:Article;
Code(s) de classement:002B03;
Mots-clés français:Vitamine D; Court terme; Exposition; Colécalciférol; Métabolisme; Animal; Rat; Cytochrome P450; Uranium appauvri;
Mots-clés anglais:Vitamin D; Short term; Exposure; Colecalciferol; Metabolism; Animal; Rat; Cytochrome P450; Depleted uranium;
Mots-clés espagnols:Vitamina D; Corto plazo; Exposición; Colecalciferol; Metabolismo; Animal; Rata; Citocromo P450; uranio empobrecido;
Localisation:INIST-7527.354000157062380020
Numéro INIST:06-0382636
© 2006 INIST-CNRS. All rights reserved.

 Résumé:
     Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D3 biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D3-target genes (ECaCI, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2rl mRNA level was increased at day 3. Cyp27al activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27bl mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels.
Misa Ristovic
Traduit par Persa Aligrudic