Back to Search Start Over

Telmisartan Plus Propranolol Improves Liver Fibrosis and Bile Duct Proliferation in the PSC-Like Abcb4−/− Mouse Model

Authors :
Hans-Michael Steffen
Heike V Hunt
Galyna Pryymachuck
Tobias Goeser
Dirk Nierhoff
I. Strack
Münevver Demir
Maria Quasdorff
Susanne Mende
Sigrid Schulte
Hans-Peter Dienes
Ulrich Töx
Margarete Odenthal
Source :
Digestive Diseases and Sciences. 58:1271-1281
Publication Year :
2012
Publisher :
Springer Science and Business Media LLC, 2012.

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to cirrhosis and cholangiocellular carcinoma. Inhibitors of the renin-angiotensin system or the sympathetic nervous system delay liver fibrogenesis in animal models.We investigated the antifibrotic potential of telmisartan, an angiotensin II type 1 receptor antagonist, and the β-adrenoceptor blocker propranolol in the PSC-like Abcb4 knockout mouse model.Sixty-five Abcb4 (-/-) mice were treated with telmisartan for 3 or 5 months (T) and with telmisartan plus propranolol for 3, 5, or 8 months (TP), or for 2 or 5 months starting with a delay of 3 months (TP delayed). Liver hydroxyproline content, inflammation, fibrosis, and bile duct proliferation were assessed; fibrosis-related molecules were analyzed by real-time polymerase chain reaction and Western blotting.Compared to controls, telmisartan monotherapy had no significant influence on hydroxyproline; however, telmisartan plus propranolol reduced hydroxyproline (TP 3 months, p = 0.008), fibrosis score (TP 3 months and TP 8 months, p = 0.043 and p = 0.008, respectively; TP delayed 8 months, p0.0005), bile duct proliferation (TP 8 months and TP delayed 8 months, p = 0.006 and p0.0005, respectively), and procollagen α1(I), endothelin-1, TIMP-1 and MMP3 mRNA as well as α-SMA, CK-19, and TIMP-1 protein.Telmisartan plus propranolol reduces liver fibrosis and bile duct proliferation in the PSC-like Abcb4 (-/-) mouse model, even when started at late stages of fibrosis, and may thus represent a novel therapeutic option for cholestatic liver diseases such as PSC.

Details

ISSN :
15732568 and 01632116
Volume :
58
Database :
OpenAIRE
Journal :
Digestive Diseases and Sciences
Accession number :
edsair.doi.dedup.....152aa76122d0b0be46890ffcce4333da
Full Text :
https://doi.org/10.1007/s10620-012-2499-3