Obstructive Liver Injury and Oxidative Stress: From Pathogenesis to Therapeutic Perspectives

Background: Cholestasis liver diseases involve impaired bile flow and the buildup of potentially harmful bile acids in liver, which damages hepatocytes and cholangiocytes. Ongoing, cholestasis triggers inflammation, oxidative stress, mitochondrial dysfunction, apoptosis and progressive liver fibrosis. Although oxidative stress is now acknowledged as a key factor in cholestatic liver injury, its connection to metabolic and inflammatory pathways and its therapeutic potential still need further investigation. Main body: This review explores the relationship between obstructive liver injury and oxidative stress, focusing on the molecular mechanisms involved and potential treatments. The buildup of bile acids leads to increased production of reactive oxygen species, lipid peroxidation, oxidative DNA damage, and mitochondrial dysfunction, which worsens cell damage and inflam-matory signals. Mitochondrial impairment disrupts energy metabolism and redox balance, while changes in fatty acid oxidation and increased glycolysis contribute to metabolic reprogramming during cholestatis. Neutrophils and other inflammatory cells can further exacerbate oxidative damage by producing reactive oxygen and nitrogen species. These processes lead to apoptosis of hepatocytes and cholangiocytes, activation of hepatic stellate cells, deposition of extracellular ma-trix, and advancement to fibrosis. The review compiles current evidence from primary sclerosing cholangitis, primary biliary cholangitis, intrahepatic cholestasis, and experimental models of ob-structive and drug- induced cholestatic liver injury. Special focus is placed on antioxidant defenses, protecting mitochondria, regulating bile acid balance, and pharmacological approaches to reduce oxidative and inflammatory damage. New treatments that target redox imbalance and enhance bile flow may offer ways to slow disease progression, especially for patients who do not respond well to standard therapies. Conclusion: Oxidative stress is central mechanistic link between bile acid ac-cumulation, inflammation, mitochondrial dysfunction, and fibrosis in cholestatic liver disease. A deeper insight into this interconnected network may aid in developing targeted antioxidant and mitochondrial therapies,improving outcomes in obstructive liver injury.