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), 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 ( Ac- 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 Ac- 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. [ABSTRACT FROM AUTHOR]