Objective: Non‐alcoholic steatohepatitis (NASH), which is a common liver disease in industrialized countries, is associated with obesity, hypertension, and type‐2 diabetes (metabolic syndrome). Since angiotensin II (ANG II) has been suggested to play an important role in liver inflammation and fibrosis, the purpose of this study was to investigate whether therapy against renin‐angiotensin system (RAS) may provide some beneficial effect in liver of an animal model of metabolic syndrome.
Methods and Procedures: For 6 months, obese Zucker rats (OZRs) were treated as follows: OZR‐group, OZR + Perindopril (P) group, OZR + Irbesartan (IRB) group, OZR + Amlodipine (AML) group, and lean Zucker rats (LZRs) group as a control. Livers were evaluated by immunohistochemistry techniques using corresponding antibodies.
Results: All treated groups showed a similar reduction in blood pressure compared to untreated OZR. Therapy either with IRB or P improves insulin sensitivity and reduces hepatic enzyme level with respect to untreated OZR. Conversely, AML failed to modify both parameters. Untreated OZR displayed higher hepatic ANG II levels and steatosis together with a marked increase in tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and transforming growth factor‐β1 (TGF‐β1) level compared to LZR. Following RAS inhibition either by P or IRB, a significant reduction (P < 0.01) in the immunostaining of TNF‐α, IL‐6 and TGF‐β1 compared to untreated OZR was observed.
Discussion: These results indicate that ANG II expression is increased in the liver of these animals with steatohepatitis. Furthermore, RAS control by either angiotensin‐converting enzyme inhibition or AT1 receptor blockade seems to provide a beneficial modulation concerning the inflammatory response to liver injury in this model. Consequently, blockade of RAS could be a new approach to prevent or to treat patients with NASH.
These results indicate that low doses of PGT ameliorate renal fibrosis and preserve renal function in this animal model of metabolic syndrome, independently of glycaemic control or effects on body weight.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.