کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2029438 | 1070586 | 2008 | 6 صفحه PDF | دانلود رایگان |
Background/aimHepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7α-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 7α-hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7α-hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients.DesignConcentrations of 7α-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 7α-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).ResultsChanges in plasma 7α-hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7α-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 7α-hydroxy-4-cholesten-3-one and cholesterol 7α-hydroxylation rates (r = 0.81, P < 0.001).ConclusionsPlasma 7α-hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7α-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.
Journal: Steroids - Volume 73, Issue 11, October 2008, Pages 1197–1202