Effects of cholestyramine on hepatic cholesterol 7alpha-hydroxylase and serum 7alpha-hydroxycholesterol in the hamster.
Cholestyramine increases activities of hepatic cholesterol 7alpha-hydroxylase and serum levels of 7alpha-hydroxycholesterol. To examine if serum 7alpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7alpha-hydroxylase activity in a dose-dependent manner, while the serum 7alpha-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7alpha-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7alpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7Alpha-hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7alpha-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.
Kuroki
S
S
Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan. syoji@surg1.med.kyushu-u.ac.jp
Naito
T
T
Chijiiwa
K
K
Tanaka
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D002792:Cholestyramine Resin / Q000493:pharmacokinetics*; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D006888:Hydroxycholesterols / Q000097:blood*; D007668:Kidney / Q000201:enzymology*; D008647:Mesocricetus / Q000097:blood*; D013250:Steroid Hydroxylases / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D006888:Hydroxycholesterols; D002792:Cholestyramine Resin; C011724:cholest-5-en-3 beta,7 alpha-diol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C029009:steroid hormone 7-alpha-hydroxylase