title: Selective aldosterone blocker ameliorates the progression of non-alcoholic steatohepatitis in rats.
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-beta 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.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kaji
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Shirai
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Aihara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Namisaki
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Kitade
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshii
authors.forename: Koji
authors.initials: K
authors.lastname: Yanase
authors.forename: Hideto
authors.initials: H
authors.lastname: Kawaratani
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Tsujimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000450:Aldosterone / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D018450:Disease Progression; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D000450:Aldosterone