Disruption of Protein Metabolism in Liver Ischemia: Role of the Antioxidant Defense Mechanism (Preprint)

BACKGROUND Liver ischemia, characterized by decreased oxygen supply, triggers oxidative stress and metabolic dysregulation. ROS generated during ischemia-reperfusion damage hepatocytes by altering protein metabolism and cellular homeostasis. The antioxidant defense system is crucial in mitigating these oxidative insults. OBJECTIVE This study aims to elucidate the molecular mechanisms by which oxidative stress affects protein metabolism during hepatic ischemia, focusing on the involvement of the antioxidant defense system. METHODS An experimental model of hepatic ischemia was established in albino rats under general anesthesia by ligation of the hepatic artery. Biochemical assays measured oxidative stress markers, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), and protein metabolism parameters. Histopathological evaluation assessed liver tissue damage. Expression of stress-related and metabolic genes was quantified by RT-PCR. Additionally, intravenous administration of Riditox, an antioxidant formulation, was used to enhance antioxidant defenses. RESULTS • On day 3 post-ischemia, lactate dehydrogenase (LDH) activity and α1- and γ-globulin concentrations increased significantly, while total protein, albumin, and β-globulin levels decreased. • Exogenous intoxication exacerbated lipid peroxidation and impaired antioxidant defenses, resulting in dysregulated protein synthesis and altered serum protein profiles. • Both 10- and 30-minute ischemia induced significant reductions in total protein and albumin, with elevated α1- and β-globulins. These alterations intensified by day 30, concomitant with increased lipid peroxidation and decreased antioxidant enzyme activities. • Riditox administration partially restored antioxidant enzyme activity and modulated protein metabolism, though some globulin fractions and LDH activity remained elevated. • A positive correlation was observed between oxidative stress intensity, antioxidant defense status, and protein metabolism disruption. CONCLUSIONS Hepatic ischemia induces oxidative stress that significantly impairs protein metabolism via compromised antioxidant defenses and activation of inflammatory pathways. Kupffer cell activation and lipid peroxidation in hepatic stellate cells are central to these processes. Enhancing antioxidant capacity through agents such as Riditox may represent a promising therapeutic strategy to mitigate ischemia-induced liver injury.