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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2323

Title: Selective aldosterone blocker ameliorates the progression of non-alcoholic steatohepatitis in rats.
Authors: Noguchi, Ryuichi
Yoshiji, Hitoshi
Ikenaka, Yasuhide
Kaji, Kosuke
Shirai, Yusaku
Aihara, Yosuke
Yamazaki, Masaharu
Namisaki, Tadashi
Kitade, Mitsuteru
Yoshii, Junichi
Yanase, Koji
Kawaratani, Hideto
Tsujimoto, Tatsuhiro
Fukui, Hiroshi
Keywords: aldosterone
selective aldosterone blocker
liver fibrosis
hepatocarcinogenesis
angiogenesis
Issue Date: Sep-2010
Publisher: Spandidos Publications
Citation: International Journal of Molecular Medicine Vol.26 No.3 pp.407-413
Abstract: Although non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), no effective therapeutic modalities have been fully established yet. Recent studies have shown that the renin-angiotensin-aldosterone-system plays an important role in NASH. The aim of our current study was to elucidate the effects of aldosterone (Ald) inhibition on the progression of NASH. In the choline-deficient L-amino acid-defined diet-induced rat NASH model, the effects of a clinically used selective Ald blocker (SAB) were elucidated in conjunction with the activated hepatic stellate cells (HSC) and neovascularization, which are both known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively. Liver fibrosis development and the glutathione-S-transferase placental form-positive pre-neoplastic lesions were both markedly attenuated by SAB along with the suppression of the activated HSC and neovascularization. SAB inhibited the hepatic expression of transforming growth factor-β 1 and also that of the vascular endothelial growth factor. Our in vitro study showed that SAB also inhibited the Ald-induced HSC proliferation and in vitro angiogenesis in a dose-dependent manner. These results indicated that Ald plays a pivotal role in the progression of NASH. Considering that SAB is already widely used in clinical practice, this drug could represent a potential new strategy against NASH in the future.
URI: http://hdl.handle.net/10564/2323
ISSN: 11073756
Appears in Collections:01111 医学科

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