Cholesterol 7α-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat

R. Racine (1) , L. Grandcolas (1) , S. Grison (1) , J. Stefani (1) , O. Delissen (1) , P. Gourmelon (1) , G. Veyssière (2) , M. Souidi (1)

1 IRSN/PSE-SANTE/SESANE/LRTOX - Laboratoire de radiotoxicologie et radiobiologie expérimentale
2 Centre d'Enseignement et de Recherche en Nutrition Humaine d'Auvergne

Depleted uranium (DU) is a radioactive heavy metal derived from the nuclear energy production. Its wide use in civilian and military items increases the risk of its environmental dissemination, and thus the risk of internal contamination of populations living in such contaminated territories. Previous studies have shown that vitamin D and cerebral cholesterol metabolisms were affected following chronic ingestion of DU. Even more than the brain, the liver is a crucial organ in cholesterol homeostasis since it regulates cholesterol distribution and elimination at body level. The aim of this work was to assess the impact of a low-level chronic ingestion of DU on hepatic cholesterol metabolism. Rats were contaminated with DU in their drinking water at a concentration of 40. mg/l for 9 months. The major effect induced by DU was a decrease of CYP7A1 specific activity (-60%) correlated with a matching decrease of its product 7α-hydroxycholesterol in the plasma. Hepatic gene expression of transporters ABC A1, ABC G5, ABC G8 and of nuclear receptor RXR was increased, whereas that of catabolism enzyme CYP7B1 was decreased. Thus, after a chronic ingestion of DU, rats experience a modulation of cholesterol catabolism but overcome it, since their cholesterolemia is preserved and no pathology is declared. © 2010 Elsevier Ltd.

Mots clés: enzymology; genetics; liver; metabolism; Sprague Dawley rat; time; Rattus; Animals; Cholesterol; Cytochrome P-450 CYP27A1; Liver; Male; Rats; Sprague-Dawley; Time Factors; Uranium; 7alpha hydroxycholesterol; ABC transporter; ABC transporter A1; ABC transporter G5; ABC transporter G8; bile acid; cholesterol; cholesterol 7alpha monooxygenase; cholesterol ester; cytochrome P450; cytochrome P450 7B1; drinking water; retinoid X receptor; unclassified drug; uranium; cholestanetriol 26 monooxygenase; animal experiment; animal tissue; article; catabolism; cholesterol blood level; cholesterol metabolism; cholesterol synthesis; cholesterol transport; controlled study; enzyme activity; gene expression regulation; hypercholesterolemia; ingestion; liver metabolism; long term exposure; male; modulation; nonhuman; nucleotide sequence; rat; transcription regulation; water contamination; animal; drug effect

Domaines: Sciences du Vivant [q-bio]

R. Racine, L. Grandcolas, S. Grison, J. Stefani, O. Delissen, et al.. Cholesterol 7α-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat. Journal of Steroid Biochemistry and Molecular Biology, 2010, 120 (1), pp.60-66. ⟨10.1016/j.jsbmb.2010.03.066⟩. ⟨hal-02974270⟩