Document Detail


Cholesterol 7alpha-hydroxylase (CYP7A1) activity is modified after chronic ingestion of depleted uranium in the rat.
MedLine Citation:
PMID:  20362056     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 40mg/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 7alpha-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.
Authors:
R Racine; L Grandcolas; S Grison; J Stefani; O Delissen; P Gourmelon; G Veyssi?re; M Souidi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  120     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-30     Completed Date:  2010-05-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  60-6     Citation Subset:  IM    
Affiliation:
Institute for Radiological Protection and Nuclear Safety (IRSN), Laboratory of Experimental Toxicology (LRTOX), BP 17, F-92262 Fontenay-aux-Roses Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cholesterol / metabolism*
Cytochrome P-450 CYP27A1 / genetics,  metabolism*
Liver / drug effects*,  enzymology*
Male
Rats
Rats, Sprague-Dawley
Time Factors
Uranium / pharmacology*
Chemical
Reg. No./Substance:
57-88-5/Cholesterol; 7440-61-1/Uranium; EC 1.14.-/Cytochrome P-450 CYP27A1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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