Blockade of the renin-angiotensin system as a therapeutic target of NAFLD: results of an experimental model of hypercholesterolemia

Abstract

Abstract Background/Introduction Non-alcoholic fatty liver disease (NAFLD) is often associated with metabolic syndrome (MS) and its components, including systemic arterial hypertension (SAH). In a recently published meta-analysis, the estimated prevalence of SAH in patients with NAFLD was 39.34%. Recently published observational studies have shown that the presence of NAFLD is independently associated with an increased risk of identifying SAH. Therefore, we can infer that we will often have to treat SAH in patients with NAFLD and that potential beneficial effects of the antihypertensive drug, in this context, may influence the choice of the respective drug. Purpose To evaluate the effects of olmesartan in an animal model of NAFLD (hypercholesterolemic rabbits). Methods 34 rabbits divided into 3 groups: control group (CG) n=13, olmesartan group (OG) n=12 and normal control group (NCG) n=9. The NCG received standard chow for laboratory rabbits, the CG and OG received standard chow plus 1% cholesterol. The OG was medicated with olmesartan 1 mg/kg/day throughout the study period (8 weeks), and the three groups were euthanised in the eighth week. Serum levels of glucose, total cholesterol, triglycerides, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase were evaluated at baseline and euthanasia, and liver tissue samples were taken in the euthanasia from the three groups. Haematoxylin-eosin stained slides were analysed based on the histological scoring system for NAFLD, Gomori,s trichrome stained slides were used for further evaluation of fibrosis, and immunostained slides with antibodies anti-nitric oxide synthase inducible (iNOS) for hepatic oxidative stress analysis. Results The steatosis (p=0.013), lobular inflammation (p<0.001), ballooning (p=0.039), and fibrosis (p=0.015) scores were significantly lower in the OG compared to the CG. Similarly, NAFLD activity scores were significantly lower in OG compared to CG. The hepatic expression of iNOS was significantly lower in OG than CG (P=0.001). The serum variables results suggest no direct effect of olmesartan in any of them. Conclusion(s) Olmesartan significantly attenuated hepatic oxidative stress, the development of steatosis, lobular inflammation, ballooning, fibrosis and steatohepatitis. Therefore, it suggests that olmesartan may be considered a potentially suitable option for hypertensive patients with NAFLD. Funding Acknowledgement Type of funding sources: None.