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Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat

  • Inorganic Compounds
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Abstract

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 (ECaC1, 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, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 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.

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Abbreviations

1,25(OH)2D3 :

1α,25-dihydroxyvitamin D3

25(OH)D3 :

25-hydroxyvitamin D3

CaBP-D9k:

Calbindin-D9k

CAR:

Constitutive androstane receptor

CYP:

Cytochrome P450

DU:

Depleted uranium

ECaC1:

Epithelial Ca2+ channel 1

HNF:

Hepatocyte nuclear factor

PPAR:

Peroxisome proliferator activated receptor

PTH:

Parathyroid hormone

PXR:

Pregnane X receptor

RXR:

Retinoid X receptor

VDR:

Vitamin D receptor

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Acknowledgments

The authors thank C. Baudelin and N. Dudoignon for animal’s experimentation and L. Grandcolas, I. Dublineau and C. Linard for helpful assistance and invaluable advice. This study was part of the ENVIRHOM research program supported by the Institute for Radioprotection and Nuclear Safety (IRSN). J.M.A. Lobaccaro is a Professor of the Université Blaise Pascal and is supported by the Centre National de la Recherche Scientifique, the Université Blaise Pascal, the Fondation pour la Recherche Médicale #INE2000-407031/1, the Fondation BNP-Paribas.

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Authors and Affiliations

  1. 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 Cedex, France

    E. Tissandie, Y. Guéguen, F. Paquet, J. Aigueperse & M. Souidi

  2. Compared Physiology and Molecular Endocrinology, UMR Université Blaise Pascal-CNRS, 24 avenue des Landais, 6547, 63177, Aubière Cedex, France

    J. M. A. Lobaccaro

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  1. E. Tissandie
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  2. Y. Guéguen
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  3. J. M. A. Lobaccaro
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  4. F. Paquet
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  5. J. Aigueperse
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  6. M. Souidi
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Correspondence to M. Souidi.

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Tissandie, E., Guéguen, Y., Lobaccaro, J. et al. Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat. Arch Toxicol 80, 473–480 (2006). https://doi.org/10.1007/s00204-006-0068-2

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  • DOI: https://doi.org/10.1007/s00204-006-0068-2

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