Inhibition of renin–angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats

Abstract

Background/Aims: It is suggested that the renin–angiotensin system (RAS) is involved in tumor development and fibrogenesis. The aim of the present study was to examine the effect of RAS inhibition on the liver enzyme-altered preneoplastic lesions and fibrosis development. Methods: The effects of the clinically used angiotensin-I converting enzyme inhibitor (ACE-I), perindopril (PE), on two different rat model of liver carcinogenesis models induced separately by diethylnitrosamine (DEN) and a choline-deficient l-amino acid-defined (CDAA) diet were studied. This CDAA model was also used to elucidate the effect of PE on liver fibrosis development. Results: The immunohistochemical evaluation revealed that the glutathione S-transferase placental form (GST-P), and γ-glutamyltransferase (GGT)-positive preneoplastic foci significantly decreased in the livers of the PE-treated groups. In CDAA-induced liver fibrosis model, PE revealed a marked inhibitory effect of liver fibrosis development. The hepatic hydroxyproline, serum fibrosis markers, α-smooth muscle actin (α-SMA) immunopositive cells in number, and α-(III) pro-collagen mRNA expression were significantly suppressed by PE treatment. These inhibitory effects of PE were achieved even at a clinically comparable dose (2 mg/kg per day). Conclusions: These results suggested that the RAS is involved in liver carcinogenesis and fibrosis development.