Oxidative and nitrosative DNA damage in hepatic fibrosis pathogenesis in chronic viral hepatitis

Abstract

Objective. Despite a large number of studies on chronic viral hepatitis, many issues related to its pathogenesis remain unsettled. First of all, it refers to pathogenic effects of the viruses themselves, the nature and patterns of the host organism's response to the pathogen, the formation of liver cirrhosis, hepatocellular carcinoma, and several other aspects. Methods. In the serum of 150 patients with chronic viral hepatitis B and C and in the serum and in the liver homogenates taken after 31 autopsies of persons who died of cirrhosis in the outcome of chronic viral hepatitis, the total antioxidant activity was studied, the content of 8-hydroxy-2-deoxyguanosine, 8-nitroguanine, reduced glutathione, malonic dialdehyde and 4-hydroxy-2,3-nonenal. Also, the degree of DNA destruction in peripheral blood lymphocytes and hepatocytes was analyzed using the comet assay. Results. It has been established that DNA destruction of hepatocytes and peripheral blood lymphocytes is one of the leading components of the formation of hepatic fibrosis in chronic viral hepatitis B and C and can be considered as its pathognomonic marker. One of the leading mechanisms of this process can be called the enhancement of oxidative and nitrosative processes. Conclusions. There is a direct link between DNA damage and the severity of sclerotic changes in the liver. Oxidative and nitrosative stress in hepatocytes and lymphocytes causes significant violations of the integrity of membrane organelles. Biochemical changes in the liver tissue during chronic viral hepatitis B and C are generally comparable to those in the serum in all respects, which makes them promising in terms of developing algorithms for diagnosing hepatic fibrosis.