Protective Effects of Ellagic Acid Against Arsenic-Induced Hepatotoxicity in Male Wistar Rats: Impact of Heme Oxygenase-1 Upregulation

Food Sci Nutr. 2025 May 23;13(6):e70344. doi: 10.1002/fsn3.70344. eCollection 2025 Jun.

Abstract

Hepatotoxins, which may originate from chemicals, prescription medications, or medicinal plants, are a major cause of hepatotoxicity. This study aims to evaluate the protective role of ellagic acid (EA) in attenuating AsIII-induced hepatotoxicity in male rats. Forty male rats were used and divided into four groups (10 each). Group I: Negative control. Group II received 60 mg/kg/day of EA. Group III was intoxicated with AsIII at a dose of 10 mg/kg body weight for 14 days. Group IV was intoxicated with AsIII and treated daily with 60 mg/kg/day of EA, starting from Day 1 concurrently with AsIII for a total of 14 days. According to the study, AsIII intoxication (Group III) led to liver damage, as indicated by increased hepatocyte vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1) expression, and elevated serum biochemical markers-alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Hepatocyte damage was confirmed through histopathological examination. In contrast, Group IV demonstrated reduced liver damage, mild VEGF expression, HO-1 upregulation, and improvements in biochemical markers. Overall, the findings suggest that EA alleviated AsIII-induced hepatotoxicity via the HO-1 upregulation pathway, highlighting the therapeutic potential of EA in managing liver toxicity.

Keywords: HO‐1; arsenic trioxide; ellagic acid; liver toxicity; vascular endothelial growth factor.