Document Detail


Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients.
MedLine Citation:
PMID:  18582481     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIM: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7alpha-hydroxy-4-cholesten-3-one have been reported to reflect bile acid synthesis and the expression or activity of the limiting enzyme of the main biosynthetic pathway, cholesterol 7alpha-hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7alpha-hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. DESIGN: Concentrations of 7alpha-hydroxy-4-cholesten-3-one were assayed by gas-liquid chromatography: mass spectrometry in plasma samples obtained in 18 patients with primary hyperlipoproteinemia who previously underwent determination of cholesterol 7alpha-hydroxylation rates in vivo by tritium release analysis. Both determinations were performed in basal conditions and after treatment with hypolipidemic drugs (the fibric acid derivatives gemfibrozil and bezafibrate, cholestyramine alone or associated with simvastatin). RESULTS: Changes in plasma 7alpha-hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7alpha-hydroxylation rates during treatment with fibrates, cholestyramine and cholestyramine plus simvastatin. When plotting determinations from all studies (n=40), a very strict correlation was disclosed between plasma 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates (r=0.81, P<0.001). CONCLUSIONS: Plasma 7alpha-hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic subjects and therefore stands as a reliable marker of global bile acid synthesis. In view of the correlation observed, these data may help to interpret changes of plasma levels of this metabolite in terms of cholesterol balance quantification.
Authors:
Marco Bertolotti; Marina Del Puppo; Chiara Gabbi; Federica Corna; Lucia Carulli; Elisa Pellegrini; Lisa Zambianchi; Claudia Anzivino; Matteo Ricchi; Paola Loria; Marzia Galli Kienle; Nicola Carulli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-06
Journal Detail:
Title:  Steroids     Volume:  73     ISSN:  0039-128X     ISO Abbreviation:  Steroids     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-07-15     Completed Date:  2008-10-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0404536     Medline TA:  Steroids     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1197-202     Citation Subset:  IM    
Affiliation:
Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Modena, Italy. bertolotti.marco@unimore.it
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MeSH Terms
Descriptor/Qualifier:
Aged
Anticholesteremic Agents / administration & dosage
Antilipemic Agents / administration & dosage
Bezafibrate / administration & dosage
Cholestenones / metabolism*
Cholesterol / metabolism
Cholesterol 7-alpha-Hydroxylase / metabolism*
Cholestyramine Resin / administration & dosage
Complement C4 / metabolism
Data Interpretation, Statistical
Female
Gemfibrozil / administration & dosage
Humans
Hypercholesterolemia / blood,  diagnosis
Hyperlipidemias / blood*,  diagnosis,  metabolism*
Kinetics
Male
Middle Aged
Reference Standards
Simvastatin / administration & dosage
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Antilipemic Agents; 0/Cholestenones; 0/Complement C4; 11041-12-6/Cholestyramine Resin; 25812-30-0/Gemfibrozil; 3862-25-7/7 alpha-hydroxy-4-cholesten-3-one; 41859-67-0/Bezafibrate; 57-88-5/Cholesterol; 79902-63-9/Simvastatin; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase

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


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