Protective Effects of Naringenin Against Sodium Arsenite-Induced Hepatic Injury in Mice via Nrf2 Signaling

Background and purpose: Sodium arsenite (SA) is recognized as a common mineral contaminant in drinking water, significantly affecting the cardiovascular, neuroendocrine, urinary, and digestive systems. Naringenin (NG) is a flavonoid with antioxidant and anti-inflammatory properties that can prevent liver damage caused by various factors. This study was conducted to examine the protective role of NG against SA-induced hepatotoxicity in mice. Materials and methods: In this experimental study, 28 mice were allocated into four groups: (I) Control, (II) NG (50 mg/kg), (III) SA (40 mg/L), and (IV) SA+NG. NG and SA were administered orally for five weeks. Histological changes, hepatic enzyme levels (ALT and AST), oxidative stress markers (SOD, CAT, and MDA), and inflammatory biomarkers (Nrf2 and NF-kB) were assessed using biochemical and histological methods. The data were then analyzed using one-way ANOVA and Tukey’s post hoc test in SPSS software. Results: SA caused histological damage, characterized by a significant increase in the infiltration of inflammatory cells and the accumulation of red blood cells (P< 0.001). It also significantly elevated alanine transaminase (ALT) and aspartate aminotransferase (AST) levels (P<0.05). Moreover, SA significantly upregulated nuclear factor kappa B (NF-kB) expression and downregulated nuclear factor-erythroid-2 related factor 2 (Nrf2) expression. NG reduced ALT and AST activity levels, reversed histological alterations and antioxidant capacity. Furthermore, NG enhanced catalase activity levels, superoxide dismutase (SOD) activity, and Nrf2 expression. Conclusion: SA induces hepatotoxicity by increasing oxidative stress and inflammatory responses. The administration of NG effectively mitigated the harmful effects of the imbalance of oxidative stress and antioxidant pathways and the histopathological changes observed in SA-intoxicated mice