Role of Reactive Oxygen and Nitrogen Species in Pathogenesis of Cholestasis (Experimental Study)

The pathological processes in the liver accompanied by functional failure of bile-excreting ways (cholestasis) causing hepatic and systemic failure are connected with deep damages of hepatocytes. The inflammatory injuries and oxidative stress plays important role in the liver disease progression. The aim of our study was the investigation of the impact of oxidative metabolism on the adaptive response of hepatocytes in condition of cholestasis. The investigations were carried out on 30 adult white rats. Cholestasis in rats was induced by the ligation of common bile duct under the ether anesthesia. The liver tissue was studied by Electron Paramagnetic Resonance (EPR) method. Results show that cholestatic liver injury is accompanied by disturbance of mitochondrial electron transport on NADH-dehydrogenase: ubiquinon-oxidoreductase region. The bile duct ligation initiates the accumulation of polyploidy cells in liver for repairing its functional activity through reduction oxidative metabolism and inhibition mitochondrial respiratory chain I and IV complexes. Restructuring of the genome follows violations of oxidative processes. Results of our study suggest a role of genomic duplications in the adaptation to disorders in mitochondrial respiration in conditions of cholestasis and protecting cells from oxidative stress.