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Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects

フォーマット:
論文
責任表示:
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
言語:
英語
出版情報:
Elsevier, 2008-07-07
著者名:
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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掲載情報:
European Journal of Pharmacology
ISSN:
0014-2999  CiNii Articles  Webcat Plus  JAIRO
巻:
588
通号:
2-3
バージョン:
author
概要:
金沢大学大学院医学系研究科<br />金沢大学医薬保健研究域医学系<br />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. 続きを見る
URL:
http://hdl.handle.net/2297/10979

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