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. 2000 Jun;118(6):1169-78.
doi: 10.1016/s0016-5085(00)70370-2.

An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis

J J Cho  1 , B Hocher, H Herbst, J D Jia, M Ruehl, E G Hahn, E O Riecken, D Schuppan
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An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis

J J Cho et al. Gastroenterology. 2000 Jun.

Abstract

Background & aims: Endothelin 1 induces contraction, proliferation, and collagen synthesis of hepatic stellate cells in vitro, which may be mediated via the endothelin A receptor. It is unknown if specific blockade of the endothelin A receptor inhibits hepatic fibrosis in vivo. VSports手机版.

Methods: Groups of 10-20 rats with bile duct occlusion were treated with the nonpeptide endothelin-A receptor antagonist LU 135252 at 80 mg. kg(-1). day(-1) from week 1-6 or from week 4-6, or with LU at 10 mg. kg(-1). day(-1) from week 1-6. Animals with bile duct occlusion alone and sham-operated rats without or with LU at 80 mg. kg(-1). day(-1) over 6 weeks served as controls. After 6 weeks, parameters of fibrogenesis were determined. V体育安卓版.

Results: LU treatment led to improved histology, paralleled by a dose-dependence up to 60% reduction of liver collagen, even when administered at an advanced fibrosis stage V体育ios版. This was accompanied by a decreased messenger RNA of hepatic procollagen alpha1(I) and tissue inhibitor of metalloproteinase 1, 2 major effectors of fibrosis, and of serum procollagen type III, a surrogate marker of liver fibrogenesis. .

Conclusions: Selective endothelin-A receptor blockade can dramatically reduce collagen accumulation in rat secondary biliary fibrosis, a model refractory to most potential antifibrotic agents. Endothelin-A receptor antagonists are promising antifibrotic agents in chronic liver disease VSports最新版本. .

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