title: Bile synthesis in rat models of inflammatory bowel diseases.
abstract: BACKGROUND
  A broad spectrum of hepatobiliary disorders are found in patients with inflammatory bowel diseases. The aim of the present work was to study interactions between gut and liver in experimental rat models of colitis and small bowel inflammation.
  
  
  METHODS
  Colitis was induced either by trinitrobenzene sulphonic acid or dextran sodium sulphate. Small-bowel inflammation was induced by indomethacin. Bile acid secretion, bile acid pool, and cholesterol 7-alpha hydroxylase were studied. Cholesterol 7-alpha hydroxylase protein expression was analysed in the microsomal liver fraction. As portal mediators released form the inflamed gut we measured lipopolysaccharide, tumour necrosis factor-alpha and interleukin-1beta in portal serum. The hepatic inflammatory response was evaluated by binding activity of nuclear factor-kappaB, activator protein-1 and alpha-2-macroglobulin.
  
  
  RESULTS
  Increased bile acid secretion, total bile acid content in gut and liver (bile acid pool size), and hepatic cholesterol 7-alpha hydroxylase protein and mRNA levels were found in the two colitis models associated with only a minor hepatic acute phase and cytokine response. In contrast, during indomethacin-induced small-bowel inflammation bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase decreased in parallel to a strong hepatic cytokine and acute phase response.
  
  
  CONCLUSIONS
  Colitis without portal cytokine release and acute phase reaction shows an induction of bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase. In contrast, intestinal inflammation after indomethacin treatment is associated with an acute phase response and a repression of bile acid synthesis.
authors.affiliation: Department of Internal Medicine I, University of Ulm, Ulm, Germany. nektarios.dikopoulos@uni-ulm.de
authors.forename: N
authors.initials: N
authors.lastname: Dikopoulos
authors.forename: R M
authors.initials: RM
authors.lastname: Schmid
authors.forename: M
authors.initials: M
authors.lastname: Bachem
authors.forename: K
authors.initials: K
authors.lastname: Buttenschoen
authors.forename: G
authors.initials: G
authors.lastname: Adler
authors.forename: J Y L
authors.initials: JY
authors.lastname: Chiang
authors.forename: H
authors.initials: H
authors.lastname: Weidenbach
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D007213:Indomethacin