Eprosartan Reduces Inflammation and Oxidative Stress in Ethanol-induced Hepatotoxicity

Abstract

Introduction: Eprosartan is an effective blood pressure medication that blocks the Angiotensin Type 1 (AT1) receptor. The studies conducted on Eprosartan showed anti-oxidative stress effects and modulating inflammatory mechanisms. The current research is designed to clarify and examine the possible advantageous impacts of Eprosartan against chronic ethanol-induced hepatic damage.

Methods: Twenty-four male Sprague-Dawley rats were haphazardly separated into four groups. The control group received normal saline 1 g/kg for 35 days (group 1). The EtOH group received 7 g/kg of 40% ethanol orally for 35 days (group 2). The EtOH+ EP group was pretreated with 60 mg/kg of Eprosartan dissolved in normal saline orally and, after 60 minutes, received 7 g/kg of 40% ethanol orally for 35 days (group 3). The EP group received only Eprosartan 60 mg/kg dissolved in normal saline for 35 days (group 4). The levels of biochemical parameters, oxidative stress markers, pro-inflammatory cytokines, and histopathological staining were evaluated in serum and liver tissue. The interactive behavior of Eprosartan with Tumor Necrosis Factor-α (TNF-α) protein was also explained by molecular docking.

Results: Pre-treatment with Eprosartan (60 mg/kg) notably diminished the elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Gamma-Glutamyl Transferase (GGT) enzymes, total triglyceride, cholesterol, total bilirubin, and inflammatory cytokines including TNF-α, Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) levels, which were induced by alcohol administration (p-value ≤ 0.05). In the Eprosartan pre-treated group, malondialdehyde and protein carbonyl content of liver tissue were remarkably diminished, as compared to the ethanol-induced rats. In addition, histopathological results approved the indicated finding. Molecular docking research gives insights into potential interactions of Eprosartan with TNF-α protein.

Conclusion: Our results revealed that the pre-treatment with Eprosartan (60 mg/kg) preserves against chronic alcohol-induced hepatic damage.

Keywords: Ethanol; eprosartan; ethanol-induced rats.; inflammation; liver; oxidative stress.