Ameliorative effects of humic acid on copper-induced liver injury via antioxidant and chelating mechanisms

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dc.contributor.authorCagin, Yasir Furkan
dc.contributor.authorDoğru, Feyzi
dc.contributor.authorErdogan, Mehmet Ali
dc.contributor.authorAtayan, Yahya
dc.contributor.authorBerber, Ilhami
dc.contributor.authorYıldız, Azibe
dc.contributor.authorOzhan, Onural
dc.date.accessioned2026-04-04T13:14:32Z
dc.date.available2026-04-04T13:14:32Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractThe 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<0.05). HA treatment significantly reversed these alterations. Histopathologically, severe hepatic damage induced by CuSO₄ was markedly alleviated by HA. Additionally, caspase-3 and 9 expressions were significantly upregulated in the CuSO₄ group but notably reduced with HA administration. Humic acid exhibits both chelating and antioxidant effects in alleviating copper-induced hepatotoxicity. It reduces hepatic Cu accumulation, mitigates oxidative stress and apoptosis, and alleviates liver damage. Further clinical studies are required to determine its optimal dosage, formulation, and safety for human use.
dc.identifier.doi10.5455/medscience.2025.10.287
dc.identifier.endpage1279
dc.identifier.issn2147-0634
dc.identifier.issue4
dc.identifier.startpage1272
dc.identifier.trdizinid1369834
dc.identifier.urihttps://doi.org/10.5455/medscience.2025.10.287
dc.identifier.urihttps://search.trdizin.gov.tr/tr/yayin/detay/1369834
dc.identifier.urihttps://hdl.handle.net/11616/107289
dc.identifier.volume14
dc.indekslendigikaynakTR-Dizin
dc.language.isoen
dc.relation.ispartofMedicine Science
dc.relation.publicationcategoryMakale - Ulusal Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_TR_20250329
dc.subjectToksikoloji
dc.subjectGastroenteroloji ve Hepatoloji
dc.subjectBiyokimya ve Moleküler Biyoloji
dc.titleAmeliorative effects of humic acid on copper-induced liver injury via antioxidant and chelating mechanisms
dc.typeArticle

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