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Effects of cholestyramine on hepatic cholesterol 7α‐hydroxylase and serum 7α‐hydroxycholesterol in the hamster
Author(s) -
Kuroki Syoji,
Naito Tokio,
Chijiiwa Kazuo,
Tanaka Masao
Publication year - 1999
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-999-0428-y
Subject(s) - cholestyramine , medicine , endocrinology , cholesterol , chemistry , clinical chemistry , hamster , triglyceride , enzyme assay , enzyme , biochemistry
Cholestyramine increases activities of hepatic cholesterol 7α‐hydroxylase and serum levels of 7α‐hydroxycholesterol. To examine if serum 7α‐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 7α‐hydroxylase activity in a dose‐dependent manner, while the serum 7α‐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 7α‐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 7α‐hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7α‐Hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7α‐hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7α‐hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.