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Direct renin inhibitor, aliskiren, attenuates the progression of non‐alcoholic steatohepatitis in the rat model
Author(s) -
Aihara Yosuke,
Yoshiji Hitoshi,
Noguchi Ryuichi,
Kaji Kosuke,
Namisaki Tadashi,
Shirai Yusaku,
Douhara Akitoshi,
Moriya Kei,
Kawaratani Hideto,
Fukui Hiroshi
Publication year - 2013
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12081
Subject(s) - aliskiren , steatohepatitis , renin inhibitor , renin–angiotensin system , medicine , pharmacology , endocrinology , fatty liver , disease , blood pressure
Aim Renin is a rate‐limiting enzyme of the renin–angiotensin system ( RAS ), and several reports have shown that renin plays an important role in several pathological processes. Although RAS is known to play a pivotal role in the progression of non‐alcoholic steatohepatitis ( NASH ), the role of renin is still obscure. The aim of the current study was to examine the effect of the clinically used direct renin inhibitor ( DRI ), aliskiren, on the progression of NASH in a rat model. 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 activated hepatic stellate cells ( A c‐ HSC ) and neovascularization, both of which are known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively. Results DRI exerted a marked inhibitory effect against liver fibrosis development and glutathione‐ S ‐transferase placental form ( GST ‐ P ) positive preneoplastic lesions along with suppression of the A c‐ HSC and neovascularization in a dose‐dependent manner. DRI also inhibited the hepatic expressions of transforming growth factor‐beta 1 ( TGF ‐beta 1), angiotensin‐ II ( AT‐II ) and vascular endothelial growth factor ( VEGF ). These results indicated that renin played a pivotal role in the liver fibrosis development and hepatocarcinogenesis of NASH . Conclusion Because DRI is already widely used in the clinical practice with safety, this drug may represent a potential new strategy against the progression of NASH in the future.