Hepatoprotective effects of curcumin against hydrogen peroxide–induced oxidative liver injury in rats

Abstract Background Oxidative stress and inflammation contribute to liver injury and chronic disease progression. Curcumin, the major bioactive compound of Curcuma longa , has antioxidant, anti-inflammatory, and hepatoprotective activities. This study aimed to evaluate the protective effects of curcumin against hydrogen peroxide-induced oxidative liver injury in Wistar albino rats. Methodology Twenty-four rats were divided into six groups: negative control, positive control, extract-only safety control, and three H₂O₂-exposed groups treated with the Curcuma longa extract at 50, 100, and 200 mg/kg. Oxidative stress was induced by 5% H₂O₂ in drinking water for 50 days. The dried Curcuma longa extract was suspended in 0.9% sterile saline and administered orally by gavage. Liver function markers, histopathology, and hepatic expression of SOD, IL-6, MYC, and Caspase-3 were assessed. Results H₂O₂ exposure increased ALT from 44 ± 2.0 to 1190 ± 51.1 U/L, AST from 180 ± 7.5 to 1300 ± 77.9 U/L, ALP from 60 ± 3.2 to 340 ± 18.6 U/L, and total bilirubin from 0.7 ± 0.2 to 5.0 ± 0.2 mg/dL. It also caused severe hepatic damage, including necrosis, steatotic changes, apoptosis-like alterations, and inflammatory infiltration. Gene expression analysis showed downregulation of SOD and upregulation of IL-6, MYC, and Caspase-3. Caspase-3 increased to 5.50-fold in the H₂O₂ group, confirming activation of apoptosis-related signaling. Treatment improved the biochemical and histological findings, with the strongest overall protective effect observed at 200 mg/kg. At this dose, ALT, AST, ALP, and total bilirubin decreased to 520 ± 51.1 U/L, 550 ± 77.9 U/L, 120 ± 18.6 U/L, and 2.0 ± 0.2 mg/dL, respectively. It partially restored SOD expression, reduced IL-6 and MYC expression, and decreased Caspase-3 expression to 4.10-, 2.70-, and 1.90-fold at 50, 100, and 200 mg/kg, respectively. The reductions in IL-6 and MYC did not follow a linear dose-dependent pattern. Conclusion Curcumin showed hepatoprotective effects against H₂O₂-induced oxidative liver injury through antioxidant, anti-inflammatory, anti-proliferative, and anti-apoptotic mechanisms. The strongest overall protection was observed at 200 mg/kg.