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


METHODS
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.
Bertolotti
Marco
M
Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Modena, Italy. bertolotti.marco@unimore.it
Del Puppo
Marina
M
Gabbi
Chiara
C
Corna
Federica
F
Carulli
Lucia
L
Pellegrini
Elisa
E
Zambianchi
Lisa
L
Anzivino
Claudia
C
Ricchi
Matteo
M
Loria
Paola
P
Kienle
Marzia Galli
MG
Carulli
Nicola
N
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001629:Bezafibrate / Q000008:administration & dosage; D002783:Cholestenones / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000008:administration & dosage; D003181:Complement C4 / Q000378:metabolism; D003627:Data Interpretation, Statistical; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis; D006949:Hyperlipidemias / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D019821:Simvastatin / Q000008:administration & dosage
D000924:Anticholesteremic Agents; D002783:Cholestenones; D003181:Complement C4; D000960:Hypolipidemic Agents; D002792:Cholestyramine Resin; C002656:7 alpha-hydroxy-4-cholesten-3-one; D002784:Cholesterol; D019821:Simvastatin; D002790:Cholesterol 7-alpha-Hydroxylase; D015248:Gemfibrozil; D001629:Bezafibrate