Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model.

AIM: Renin is a rate-limiting enzyme of the renin-angiotensin system (RAS), andseveral reports have shown that renin plays an important role in severalpathological processes. Although RAS is known to play a pivotal role in theprogression of non-alcoholic steatohepatitis (NASH), the role of renin is stillobscure. The aim of the current study was to examine the effect of the clinicallyused direct renin inhibitor (DRI), aliskiren, on the progression of NASH in a ratmodel.METHODS: The effects of DRI on the choline-deficient L-amino acid-defined (CDAA) diet-induced rat NASH model was examined in conjunction with the activatedhepatic stellate cells (Ac-HSC) and neovascularization, both of which are knownto play important roles in liver fibrosis development and hepatocarcinogenesis,respectively.RESULTS: DRI exerted a marked inhibitory effect against liver fibrosisdevelopment and glutathione-S-transferase placental form (GST-P) positivepreneoplastic lesions along with suppression of the Ac-HSC and neovascularizationin a dose-dependent manner. DRI also inhibited the hepatic expressions oftransforming growth factor-beta 1 (TGF-beta 1), angiotensin-II (AT-II) andvascular endothelial growth factor (VEGF). These results indicated that reninplayed a pivotal role in the liver fibrosis development and hepatocarcinogenesis of NASH.CONCLUSION: Because DRI is already widely used in the clinical practice withsafety, this drug may represent a potential new strategy against the progression of NASH in the future.;博士(医学)・甲612号・平成26年3月17日;開始ページ : 1241;終了ページ : 1250;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/23448275

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書名 Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model.
著作者等 日本肝臓学会
Douhara Akitoshi
Elsevier Science Ireland
Fukui Hiroshi
Kaji Kosuke
Kawaratani Hideto
Moriya Kei
Namisaki Tadashi
Noguchi Ryuichi
Shirai Yusaku
Yoshiji Hitoshi
Aihara Yosuke
書名別名 直接的レニン阻害薬であるアリスキレンはラットモデルにおいて非アルコール性脂肪肝炎の進行を抑制する
出版元 Wiley / The Japan Society of Hepatology
刊行年月 1997. 5-
ページ数 v.
大きさ 27 cm
ISSN 13866346
NCID AA11532834
AA11140867
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言語 英語
出版国 オランダ
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