Angiotensin System Blockers in Experimental NAFLD/MASLD: Is there a Preferential Pathway or Drug?

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD), currently known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a persistent challenge in medical practice. Its global prevalence has progressively increased, with an estimated 30.1%. NAFLD has been associated with an increased risk of developing systemic hypertension, with an estimated prevalence of hypertension among patients with this liver condition at 39.34%. However, there are no established criteria for selecting antihypertensive medications for the treatment of hypertensive patients with NAFLD. Aims: To evaluate and compare the effects of the preventive use of olmesartan and ramipril in an animal model of NAFLD. Assess the potential differences and determine if there are specific aspects that may account for these differences. In addition to histological analysis and metabolic variables, evaluate oxidative stress through immunohistochemistry. Methods: A total of 41 rabbits were distributed into four groups: normal control group (NG) with 9 animals; placebo group (PG) with 10 animals; olmesartan group (OG) with 12 animals; and ramipril group (RG) with 10 animals. The NG received a standard diet without additives, while the OG, PG, and RG were given the standard diet with added cholesterol. The OG and RG were treated with their respective medications from baseline until euthanasia over an 8-week period. Hematoxylin-eosin stained slides were assessed using a scoring system for histological evaluation of NAFLD, and hepatic oxidative stress was evaluated through immunohistochemistry. Results: There was a significant attenuation of steatosis, lobular inflammation, ballooning, fibrosis, and steatohepatitis, as indicated by the activity score, in both the ramipril group (RG) and olmesartan group (OG) compared to the placebo group (PG). Additionally, hepatic oxidative stress was notably decreased in these treatment groups. Conclusion: The preventive use of ramipril and olmesartan significantly attenuated the development of fundamental histological changes and hepatic oxidative stress in an animal model of NAFLD. Therefore, it can be inferred that olmesartan and ramipril may add benefit in the treatment of hypertensive patients with NAFLD. However, such findings require substantiation based on clinical studies.