Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Fickert, P; Zollner, G; Fuchsbichler, A; Stumptner, C; Weiglein, AH; Lammert, F; Marschall, HU; Tsybrovskyy, O; Zatloukal, K; Denk, H; Trauner, M.
Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles.
Gastroenterology. 2002; 123(4):1238-1251
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Autor/innen der Med Uni Graz:
Denk Helmut
Fickert Peter
Stumptner Cornelia
Trauner Michael
Tsybrovskyy Oleksiy
Weiglein Andreas
Zatloukal Kurt
Zollner Gernot
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Abstract:
Background & Aims: The effects of ursodeoxycholic acid (UDCA) in biliary obstruction are unclear. We aimed to determine the effects of UDCA in bile duct-ligated and in Mdr2 knockout (Mdr2(-/-)) mice with biliary strictures. Methods: Mice fed UDCA (0.5% wt/wt) or a control diet were subjected to common bile duct ligation (CBDL), selective bile duct ligation (SBDL), or sham operation. UDCA was also fed to 2-month-old Mdr2(-/-) mice. Serum biochemistry, liver histology, and mortality rates were investigated. The biliary tract was studied by plastination, India ink injection, and electron microscopy. The effects of UDCA on biliary pressure were determined by cholangiomanometry. Results: UDCA feeding in CBDL mice increased biliary pressure, with subsequent rupture of cholangioles and aggravation of hepatocyte necroses, resulting in significantly increased mortality. UDCA feeding in SBDL mice aggravated liver injury exclusively in the ligated lobe. Mdr2(-/-) mice developed liver lesions resembling sclerosing cholangitis characterized by biliary strictures and dilatations. UDCA induced bile infarcts, in these animals. Conclusions: UDCA aggravates bile infarcts and hepatocyte necroses in mice with biliary obstruction via disruption of cholangioles as a result of increased biliary pressure caused by its choleretic action.
Find related publications in this database (using NLM MeSH Indexing)
ATP-Binding Cassette Transporters - genetics
Animals -
Bile - metabolism
Bile Acids and Salts - metabolism
Cholagogues and Choleretics - pharmacology
Cholangitis, Sclerosing - mortality Cholangitis, Sclerosing - pathology Cholangitis, Sclerosing - physiopathology
Cholestasis, Extrahepatic - mortality Cholestasis, Extrahepatic - pathology Cholestasis, Extrahepatic - physiopathology
Common Bile Duct - physiopathology
Disease Models, Animal -
Infarction - chemically induced Infarction - pathology Infarction - physiopathology
Ligation -
Male -
Mice -
Mice, Knockout -
Necrosis -
P-Glycoproteins - genetics
Pressure -
Ursodeoxycholic Acid - pharmacology

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