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Cited 43 time in webofscience Cited 44 time in scopus
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Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model

Authors
Kim, Moon YoungBaik, Soon KooPark, Dong HunJang, Yoon OkSuk, Ki TaeYea, Chang JinLee, Il YoungKim, Jae WooKim, Hyun SooKwon, Sang OkCho, Mi YunKo, Sang BaikChang, Sei JinUm, Soon HoHan, Kwang-Hyub
Issue Date
Nov-2008
Publisher
SPRINGER JAPAN KK
Keywords
hepatic fibrosis; hepatic stellate cell; angiotensin II receptor blocker; angiotensin converting enzyme inhibitor
Citation
JOURNAL OF GASTROENTEROLOGY, v.43, no.11, pp.889 - 896
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF GASTROENTEROLOGY
Volume
43
Number
11
Start Page
889
End Page
896
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/16719
DOI
10.1007/s00535-008-2239-9
ISSN
0944-1174
Abstract
Angiotensin blockade such as with an angiotensin II receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) has antifibrotic properties. The aim of this study was to evaluate and compare the antifibrotic effect between ARBs and ACEIs. Common bile duct-ligated (BDL) adult Sprague-Dawley rats were allocated to five groups (each group, n = 8) as follows: G1, BDL without drug; G2, BDL + captopril 100 mg/kg per day; G3, BDL + ramipril 10 mg/kg per day; G4, BDL + losartan 10 mg/kg per day; G5, BDL + irbesartan 15 mg/kg per day. Four weeks post-BDL, hepatic fibrosis was analyzed histomorphologically using Batts and Ludwig scores. alpha-Smooth muscle actin (alpha-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor beta (TGF-beta) expressions were evaluated by real-time reverse transcriptase-polymerase chain reaction. Angiotensin receptor expression was also determined by Western blotting. Batts and Ludwig scores were 3.8, 2.6, 2.4, 1.8, and 1.6 in G1, G2, G3, G4, and G5, respectively. Histologically, ARB groups (G4, G5) showed significant suppression of hepatic fibrosis compared with ACEI groups or the control. Expressions of alpha-SMA (%) and the content of hydroxyproline (mu g liver tissue) were significantly lower in ARB groups (G4, G5) than in ACEI groups (G2, G3) (P < 0.05). Also, ARB reduced the expression of angiotensin receptor, collagen, procollagen, and TGF-beta 1 compared with ACEI. Western blot analysis showed that the expression of angiotensin receptor was inhibited in both ARB and ACEI groups. Both ARB and ACEI attenuate hepatic fibrosis through inhibiting hepatic stellate cell activation, and the inhibitory effect of ARBs on hepatic fibrosis is superior to that of ACEIs in the BDL rat model.
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