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- Title
Telmisartan Plus Propranolol Improves Liver Fibrosis and Bile Duct Proliferation in the PSC-Like Abcb4 Mouse Model.
- Authors
Mende, Susanne; Schulte, Sigrid; Strack, Ingo; Hunt, Heike; Odenthal, Margarete; Pryymachuck, Galyna; Quasdorff, Maria; Demir, Münevver; Nierhoff, Dirk; Dienes, Hans-Peter; Goeser, Tobias; Steffen, Hans-Michael; Töx, Ulrich
- Abstract
Background: 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. Aims: 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. Methods: 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. Results: 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, p < 0.0005), bile duct proliferation (TP 8 months and TP delayed 8 months, p = 0.006 and p < 0.0005, respectively), and procollagen α1(I), endothelin-1, TIMP-1 and MMP3 mRNA as well as α-SMA, CK-19, and TIMP-1 protein. Conclusions: 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.
- Subjects
BENZOATES; PROPRANOLOL; FIBROSIS; BILE ducts; LIVER disease treatment; RENIN-angiotensin system; ANIMAL models in research; ADRENERGIC receptors; THERAPEUTICS
- Publication
Digestive Diseases & Sciences, 2013, Vol 58, Issue 5, p1271
- ISSN
0163-2116
- Publication type
Article
- DOI
10.1007/s10620-012-2499-3