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

Written by Mikhaylov А.О., Popov A.F., Ivanis V.A., Khamueva E.V., Ivanova N.S., Simakova A.I.

  UDK: 616.36–002.2–06:616.36–002.17–074 | Pages: 63–70 | Full text PDF | Open PDF 


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.

Links to authors:

А.О. Mikhaylov1, A.F. Popov2, V.A. Ivanis2, E.V. Khamueva1, N.S. Ivanova2, A.I. Simakova2
1 Regional Clinical Hospital No. 2 (55 Russkaya St. Vladivostok 690105 Russian Federation),
2 Pacific State Medical University (2 Ostryakova Ave. Vladivostok 690002 Russian Federation)

1. Kropotov A.V., Chelomin V.P., Slobodskova V.V. [et al.]. Estimating carbon tetrachloride toxicity and protective action of silibinin and haurantin using DNA-comet assay in rat liver // Pacific Medical Journal. 2013. No. 2. P. 63–66.
2. Mikhaylov A.O., Popov A.F., Ivanova N.S. [et al.]. Destruction, oxidation of DNA and lipids of mitochondrial membranes in chronic viral hepatitis C, B // Infectious Diseases. 2018. Vol. 16, No. 1. P. 15–21.
3. Mikhaylov A.O., Popov A.F., Ivanova N.S., Simakova A.I. The investigation of DNA damage in lymphocytes by comet assay in chronic viral hepatitis B patients // Epidemiology and Infectious Diseases. 2017. Vol. 22, No. 2. P. 64–68.
4. Mikhaylov A.O., Popov A.F., Ivanova N.S., Simakova A.I. DNA damage in lymphocytes in chronic viral hepatitis B, C // Journal Infectology. 2017. Vol. 9, No. 2. P. 29–36.
5. Popov A.F., Mikhaylov A.O., Ivanova N.S., Simakova A.I. Method of DNA-comet assay in the diagnosis of liver fibrosis in patients with chronic viral hepatitis C // Epidemiology and Infectious Diseases. 2015. Vol. 20, No. 2. P. 29–33.
6. Chernigina I.A., Shcherbatyuk T.G. A new version of comet assay // Modern Technologies in Medicine. 2016. Vol. 8, No. 1. P. 20–27.
7. Bolukbas C., Bolukbas F.F., Kocyigit A. [et al.]. Relationship between levels of DNA damage in lymphocytes and histopathological severity of chronic hepatitis C and various clinical forms of hepatitis B // J. Gastroenterol. Hepatol. 2006. Vol. 21, No. 3. P. 610–616.
8. Cao L., Quan Xi-B., Zeng W.-J. [et al.]. Mechanism of hepatocyte apoptosis // J. Cell Death. 2016. No. 9. P. 19–29.
9. Grossi S., Sumberaz A., Gosmar M. [et al.]. DNA damage in peripheral blood lymphocytes of patients with cirrhosis related to alcohol abuse or to hepatitis B and C viruses // Eur. J. Gastroenterol. Hepatol. 2008. Vo. 20, No. 1. P. 22–25.
10. Ivanov A.I., Valuev–Elisston V.T., Tyurina D.A. [et al.]. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis // Oncotarget. 2017. Vol. 8, No. 3. P. 3895–3932.
11. Iwakiri Ya. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase // Clin. Mol. Hepatol. 2015. Vol. 21, No. 4. P. 319–325.
12. Iwakiri Ya., Kim M.Y. Nitric oxide in liver diseases // Trends Pharmacol. Sci. 2015. Vol. 36, No. 8. P. 524–536.
13. Kawanishi S., Ohnishi S., Ma N. [et al.]. Nitrative and oxidative DNA damage in infection-related carcinogenesis in relation to cancer stem cells // Genes and Environment. 2016. doi: 10.1186/ s41021-016-0070-8 (date of access: 03.08.2018).
14. Li P., Ramm G.A., Macdonald G.A. Value of the 8-oxodG/dG ratio in chronic liver inflammation of patients with hepatocellular carcinoma // Redox Biology. 2016. doi: 10.1016/j.redox.2016.02.003 (date of access: 03.08.2018).
15. Olive P.L., Banáth J.P. The comet assay: a method to measure DNA damage in individual cells // Nature Protocols. 2006. Vol. 1, No. 1. P. 23–29.


Founded in 1997  |  Editions in a year: 4, Articles in one issue: 30 |  ISSN of print version: 1609-1175  |  Ind.: 18410 (Agency "Rospechat’")  |  Edition: 1000 c.