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Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects
http://hdl.handle.net/2297/10979
http://hdl.handle.net/2297/109791e559c4a-08c4-4091-88cd-d5ec58bd1102
名前 / ファイル | ライセンス | アクション |
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ME-PR-KURITA-S-316.pdf (610.5 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-03 | |||||
タイトル | ||||||
タイトル | Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kurita, Seiichiro
× Kurita, Seiichiro× Takamura, Toshinari× Ota, Tsuguhito× Matsuzawa-Nagata, Naoto× Kita, Yuki× Uno, Masafumi× Nabemoto, Satoko× Ishikura, Kazuhide× Misu, Hirofumi× Ando, Hitoshi× Zen, Yoh× Nakanuma, Yasuni× Kaneko, Shuichi |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学大学院医学系研究科 | |||||
提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学医薬保健研究域医学系 | |||||
書誌情報 |
European Journal of Pharmacology 巻 588, 号 2-3, 発行日 2008-07-07 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0014-2999 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00639687 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.ejphar.2008.04.028 | |||||
出版者 | ||||||
出版者 | Elsevier | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-β, α1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis. © 2008 Elsevier B.V. All rights reserved. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |