Cholestyramine alters bile acid amounts and the expression of cholesterol-related genes in rabbit intestinal and hepatic tissues
2017
OBJECTIVE
Cholestyramine, as a bile acid sequestering exchange resin, has been wildly used to treat hypercholesterolemia. The aim of this study was to explore how cholestyramine regulated serum cholesterol amounts and bile acid levels in animal models.
METHODS
The New Zealand White rabbits were randomly assigned to the control (given distilled water) and cholestyramine (CHO)-treated (given cholestyramine 1 g/kg/day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were generated in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase (CYP7A1), short heterodimer partner (SHP), bile salt export pump (BSEP), ileal bile acid-binding protein (IBABP), and LDL receptor (LDL-R) mRNA expressions were assessed by real-time polymerase chain reaction (RT-PCR). CYP7A1 activity was also determined.
RESULS
Cholestyramine treatment decreased serum cholesterol levels by 12.1%. Although cholestyramine did not change bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, cholestyramine also significantly increased CYP7A1 expression and activity, as well as IBABP and LDL-R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions.
Conclusion
Cholestyramine markedly alters bile acid and cholesterol amounts in rabbit intestinal and hepatic tissues, downregulating genes responsible for cholesterol homeostasis.
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