Effects of cholestyramine on hepatic cholesterol 7 alpha-hydroxylase and serum 7 alpha-hydroxycholesterol in the hamster

Cholestyramine increases activities of hepatic cholesterol 7 alpha-hydroxyl ase and serum levels of 7 alpha-hydroxycholesterol. To examine if serum 7 a lpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hams ters 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 s tudy, hepatic and serum cholesterol levels were significantly decreased dos e-dependently when more than 0.5% of cholestyramine was fed for 28 d. Chole styramine increased the cholesterol 7 alpha-hydroxylase activity in a dose- dependent manner, while the serum 7 alpha-hydroxycholesterol level was esse ntially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum ch olesterol levels markedly decreased when 2% cholestyramine was fed for long er than 3 d. The serum triglyceride level increased significantly for the f irst 7 d and then decreased. Cholesterol 7 alpha-hydroxylase activity incre ased 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 7 a lpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7 alpha-Hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride le vels. We conclude that the serum 7 alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7 alpha-hydroxylase, whe n cholesterol metabolism is severely disturbed by cholestyramine.