Background/aim: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7 -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 7 -hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7 -hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. Design: Concentrations of 7 -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 7 - 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 7 -hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7 -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 7 -hydroxy-4-cholesten-3-one and cholesterol 7 -hydroxylation rates (r = 0.81, P < 0.001). Conclusions: Plasma 7 -hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7 -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. © 2008 Elsevier Inc. All rights reserved.

Bertolotti, M., DEL PUPPO, M., Gabbi, C., Corna, F., Carulli, L., Pellegrini, E., et al. (2008). Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients. STEROIDS, 73(11), 1197-1202 [10.1016/j.steroids.2008.05.011].

Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients

DEL PUPPO, MARINA;KIENLE, MARZIA DONATELLA;
2008

Abstract

Background/aim: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7 -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 7 -hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7 -hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. Design: Concentrations of 7 -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 7 - 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 7 -hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7 -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 7 -hydroxy-4-cholesten-3-one and cholesterol 7 -hydroxylation rates (r = 0.81, P < 0.001). Conclusions: Plasma 7 -hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7 -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. © 2008 Elsevier Inc. All rights reserved.
Articolo in rivista - Articolo scientifico
Bile acid synthesis; Cholesterol 7 -hydroxylation; Cholesterol homeostasis; 7 -Hydroxy-4-cholesten-3-one; Hyperlipoproteinemia; Hypolipidemic drugs
English
2008
73
11
1197
1202
none
Bertolotti, M., DEL PUPPO, M., Gabbi, C., Corna, F., Carulli, L., Pellegrini, E., et al. (2008). Correlation between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates in vivo in hyperlipidemic patients. STEROIDS, 73(11), 1197-1202 [10.1016/j.steroids.2008.05.011].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/1752
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