Discovering the Hepatoprotective Properties of Ara290 in Acetaminophen-Induced Liver Toxicity Publisher



Ghassemi Barghi N¹ ; Fazeli R² ; Fakhri MSB^{1, 3} Show Affiliations
Source: Applied In Vitro Toxicology Published:2025

Abstract

Introduction: Erythropoietin (EPO), known for its hematopoietic function, also has anti-inflammatory, antiapoptotic, antioxidant, and cytoprotective effects. ARA290, a peptide derived from EPO, selectively interacts with the innate repair receptor and exhibits similar properties. ARA290 offers tissue protection like EPO but without the hematopoietic side effects that limit EPO’s clinical use. In vitro, bioassays are important in evaluating new agents with hepatoprotective effects. This study aimed to assess the effect of ARA290 pretreatment on acetaminophen (APAP)-induced damage in HepG2 cells. Materials and Methods: In this study, we explored the potential of ARA290 as a hepatoprotective agent, specifically looking at its ability to moderate the cytotoxicity, genotoxicity, inflammation, and oxidative stress triggered in vitro by APAP. We evaluated the impact of ARA290 on APAP-induced toxicity in HepG2 cells. The cells were pretreated with ARA290 (50-400 nM) and APAP (2-8 mM). We assessed the activities of hepatic enzymes such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. The 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazoliumbromide (MTT) assay was used to evaluate cytotoxicity, while the micronucleus test and comet assay were employed to assess the genoprotective effect of ARA290. Results: ARA290 significantly decreased the percentage of DNA in the tail and the frequency of micronuclei induced by APAP. Besides, APAP was found to impair antioxidant defense and hepatic enzyme activities and induce inflammation and apoptotic cell death. ARA290 effectively mitigated APAP-induced oxidative stress, moderated enzyme activity, and protected against APAP-induced inflammation and apoptotic cell death. Discussion and Conclusion: These findings suggest that ARA290 has potential as a novel hepatoprotective agent. In conclusin our findings provided the first evidence of the potential geno/chemoprotective applications of ARA290 in hepatotoxicity and liver failure. Copyright 2025, Mary Ann Liebert, Inc., publishers.