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SHR Neuro Krebs Kardio Lipid

Fickert, P; Fuchsbichler, A; Marschall, HU; Wagner, M; Zollner, G; Krause, R; Zatloukal, K; Jaeschke, H; Denk, H; Trauner, M.
Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice.
Am J Pathol. 2006; 168(2):410-422 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Denk Helmut
Fickert Peter
Krause Robert
Trauner Michael
Wagner Martin
Zatloukal Kurt
Zollner Gernot
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Number of Figures: 14
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Abstract:
We determined the mechanisms of hepatobiliary injury in the lithocholic acid (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days), followed by assessment of liver morphology and ultrastructure, tight junctions, markers of fibrosis and key proteins of hepatobiliary function, and bile flow and composition. As expected LCA feeding led to bile infarcts, which were followed by a destructive cholangitis with activation and proliferation of periductal myofibroblasts. At the ultrastructural level, small bile ducts were frequently obstructed by crystals. Biliary-excreted fluorescence-labeled ursodeoxycholic acid accumulated in bile infarcts, whereas most infarcts did not stain with India ink injected into the common bile duct; both findings are indicative of partial biliary obstruction. Expression of the main basolateral bile acid uptake proteins (sodium-taurocholate cotransporter and organic anion-transporting polypeptide 1) was reduced, the canalicular transporters bile salt export pump and multidrug-related protein 2 were preserved, and the basolateral transporter multidrug-related protein 3 and the detoxifying enzyme sulfotransferase 2a1 were induced. Thus, we demonstrate that LCA feeding in mice leads to segmental bile duct obstruction, destructive cholangitis, periductal fibrosis, and an adaptive transporter and metabolic enzyme response.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Bile Acids and Salts - metabolism
Biliary Tract Diseases - chemically induced Biliary Tract Diseases - metabolism Biliary Tract Diseases - pathology
Cholangitis - chemically induced Cholangitis - metabolism
Cholestasis - chemically induced Cholestasis - metabolism Cholestasis - pathology
Detergents - toxicity
Diet -
Drug-Induced Liver Injury -
Fibrosis - chemically induced Fibrosis - metabolism Fibrosis - pathology
Fluorescence -
Lithocholic Acid - toxicity
Liver - drug effects Liver - injuries Liver - metabolism
Liver Diseases - metabolism Liver Diseases - pathology
Male -
Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism
Mice -
Mice, Inbred C57BL -
Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism
Organic Anion Transporters - genetics Organic Anion Transporters - metabolism
Organic Anion Transporters, Sodium-Dependent - genetics Organic Anion Transporters, Sodium-Dependent - metabolism
RNA, Messenger - genetics RNA, Messenger - metabolism
Reverse Transcriptase Polymerase Chain Reaction -
Sulfotransferases - genetics Sulfotransferases - metabolism
Symporters - genetics Symporters - metabolism

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