Inhibition of intestinal bile acid absorption by ASBT inhibitor A4250 protects against cholestatic liver and bile duct injury in MDR2-/- mouse model of sclerosing Cholangitis
CD Fuchs, A Baghdasaryan, CH Österreicher, U Lemberger, H Graffner, E Krones, P Fickert, A Wahlström, H Marschall, G Paumgartner, M Trauner · Zeitschrift für Gastroenterologie · 2015 · Heft 05
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Zusammenfassung
Background and Aims: Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Methods: 8-week-old Mdr2-/- (Abcb4-/-) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) – a highly potent and selective ASBT inhibitor – or a chow diet. Liver injury was assessed biochemically and…
