Abstract

The liver plays a critical role in metabolism, detoxification, and maintaining internal homeostasis. Excessive accumulation of copper (Cu), a metal with known toxic effects, can cause severe hepatic injury, particularly in genetic disorders such as Wilson’s disease. This study aimed to investigate the chelating and antioxidant properties of humic acid (HA) in mitigating Cu-induced toxicity, oxidative damage, and apoptosis in an experimental model. Forty male rats were randomly assigned to four groups (n=10). Group I received a standard diet (Control); Group II received HA, 536 mg/kg/day, oral); Group III was administered copper sulfate (CuSO₄, 75 mg/kg/day, oral); Group IV received both HA and CuSO₄ for 14 days. Blood and liver tissue samples were collected post-euthanasia for biochemical, histopathological, and immunohistochemical analyses. Biochemical parameters included alanine aminotransferase (ALT), aspartate aminotransferase (AST), copper (Cu), ceruloplasmin, malondialdehyde (MDA), oxidative stress index (OSI), total antioxidant status (TAS), total oxidant status (TOS), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Caspase-3 and 9 expressions were evaluated immunohistochemically. The CuSO₄ group showed significantly increased ALT, AST, and Cu levels, alongside elevated MDA and TOS, and reduced TAS, GSH, SOD, CAT, and GPx levels (p

Key words: Humic acid, copper toxicity, oxidative stress, hepatotoxicity, chelation, apoptosis, rat model