title: Cholestyramine alters bile acid amounts and the expression of cholesterol-related genes in rabbit intestinal and hepatic tissues.
abstract: OBJECTIVE
  Cholestyramine (CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models.
  
  
  METHODS
  New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1 ), small 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. CYP7A1 activity was also determined.
  
  
  RESULTS
  CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions.
  
  
  CONCLUSIONS
  CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis.
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Dong Ni
authors.initials: DN
authors.lastname: Qiu
authors.affiliation: GI Lab VA Medical Center, East Orange, New Jersey, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Da Yu
authors.initials: DY
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wei Qun
authors.initials: WQ
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhong Guang
authors.initials: ZG
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wei Ru
authors.initials: WR
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Jiang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000837:Anion Exchange Resins / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005243:Feces / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000837:Anion Exchange Resins; D001647:Bile Acids and Salts; D050556:Fatty Acid-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; C099713:nuclear receptor subfamily 0, group B, member 2; D002792:Cholestyramine Resin; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase
keywords: bile acid; cholesterol; cholesterol 7α-hydroxylase; cholestyramine