{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T09:44:24Z","timestamp":1762249464444},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,21]],"date-time":"2013-07-21T00:00:00Z","timestamp":1374364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin\u2013angiotensin system (<jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>) appears to play important roles in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>. Direct renin inhibitors (<jats:styled-content style=\"fixed-case\">DRI<\/jats:styled-content>) reduce plasma renin activity (<jats:styled-content style=\"fixed-case\">PRA<\/jats:styled-content>) through interaction with the active site of the enzyme and reduce the formation of angiotensin\u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">AT\u2010II<\/jats:styled-content>). Therefore, the <jats:styled-content style=\"fixed-case\">DRI<\/jats:styled-content> aliskiren may further suppress the <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>. This study examined the effects of aliskiren on <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> in fatty liver <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>hionogi (<jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>)\u2010<jats:italic>ob\/ob<\/jats:italic> male mice that are the closest animal model of metabolic syndrome\u2010related <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Aliskiren (100\u2009mg\/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight <jats:styled-content style=\"fixed-case\">FLS<\/jats:styled-content>\u2010<jats:italic>ob\/ob<\/jats:italic> mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Amounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of \u03b1\u2010smooth muscle actin positivity, the numbers of F4\/80 positive, 8\u2010hydroxy\u20102\u2010deoxyguanosine positive cells and immunohistochemical staining of 4\u2010hydroxynonenal were also significantly decreased in the aliskiren group. Levels of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression for transforming growth factor\u2010\u03b21, connective tissue growth factor and monocyte chemoattractant protein\u20101 were significantly lower in the aliskiren group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Aliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12186","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T12:14:41Z","timestamp":1371557681000},"page":"888-896","source":"Crossref","is-referenced-by-count":16,"title":["Therapeutic effects of the direct renin inhibitor, aliskiren, on non\u2010alcoholic steatohepatitis in fatty liver <scp>S<\/scp>hionogi <i>ob\/ob<\/i> male mice"],"prefix":"10.1111","volume":"44","author":[{"given":"Manabu","family":"Kishina","sequence":"first","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Koda","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiho","family":"Tokunaga","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomitsu","family":"Matono","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Ueki","sequence":"additional","affiliation":[{"name":"Division of Medicine and Clinical Science Department of Multidisciplinary Internal Medicine Faculty of Medicine Tottori University  Yonago 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