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. 2013 Jul;43(7):765-74.
doi: 10.1111/hepr.12008. Epub 2012 Nov 20.

Dual blockade of angiotensin-II and aldosterone suppresses the progression of a non-diabetic rat model of steatohepatitis

Ryuichi Noguchi  1 , Hitoshi Yoshiji, Yasuhide Ikenaka, Kosuke Kaji, Yosuke Aihara, Yusaku Shirai, Tadashi Namisaki, Mitsuteru Kitade, Akitoshi Douhara, Kei Moriya, Hiroshi Fukui
Affiliations

Dual blockade of angiotensin-II and aldosterone suppresses the progression of a non-diabetic rat model of steatohepatitis

Ryuichi Noguchi et al. Hepatol Res. 2013 Jul.

Abstract

Aim: Both angiotensin-II (AT-II) and aldosterone (Ald) play pivotal roles in the pathogenesis of diseases in several organs including the liver. We previously reported that suppression of AT-II and Ald with angiotensin-converting enzyme inhibitor (ACE-I) and selective Ald blocker (SAB), respectively, attenuated the rat liver fibrogenesis and hepatocarcinogenesis. The aim of our current study was to elucidate the combined effects of ACE-I and SAB in the progression of a non-diabetic rat model of steatohepatitis, and the possible mechanisms involved.

Methods: In the choline-deficient L-amino acid-defined (CDAA) diet-induced model, the effects of ACE-I and SAB on liver fibrosis development and hepatocarcinogenesis were elucidated, especially in conjunction with neovascularization.

Results: Treatment with both ACE-I and SAB suppressed the development of liver fibrosis and glutathione-S-transferase placental form (GST-P) positive pre-neoplastic lesions. The combined treatment with both agents exerted more inhibitory effects as compared with either a single agent along with suppression of the activated hepatic stellate cells (Ac-HSC) and neovascularization, both of which play important roles in these processes. Our in vitro study showed that AT-II type 1 receptor blocker (ARB) and SAB inhibited Ac-HSC proliferation and in vitro angiogenesis along with suppression of the in vivo studies.

Conclusion: Dual blockade of AT-II and Ald suppresses the progression of a non-diabetic rat model of steatohepatitis. Because both agents are widely and safely used in clinical practice, this combination therapy could be an effective new strategy against steatohepatitis in the future.

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