Effect of oligoribonucleotides with D-mannitol complexes on oxidative stress indicators against thioacetamide-induced liver fibrosis

Authors

  • Tetiana Marchyshak Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0001-7141-1198
  • Tetiana Yakovenko Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0002-7296-5755
  • Zenoviy Tkachuk Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143, Ukraine https://orcid.org/0000-0002-0433-007X

DOI:

https://doi.org/10.15587/2519-8025.2020.214418

Keywords:

oxidative stress, antioxidant defence system, complexes of oligoribonucleotides with D-mannitol, liver fibrosis

Abstract

The aim of the study. To determine the effect of oligoribonucleotides-D-mannitol complexes (ORN-D-M) on the indicators of oxidative destruction of biomolecules and the antioxidant system of cells in thioacetamide (TAA)-induced liver fibrosis.

Materials and methods. Liver fibrosis was induced for 8 weeks by intraperitoneal administration of TAA (150 mg/kg body weight). ORN-D-M (200 mg/kg per os) was administered orally during intoxication. At the end of the experiment, the liver was excised and examined for the content of oxidative stress products and the activity of antioxidant enzymes. Data were analyzed using the ANOVA test followed by Tukey post hoc testing.

Results. It is shown that the monotherapeutic treatment of ORN-D-M in TAA-induced liver fibrosis has a pronounced protective effect, which is manifested in the reduction of oxidative stress. ORN-D-M led to the attenuation of free radical damage of biopolymers, which was manifested in a decrease in the levels of peroxidation products of lipids and proteins with a simultaneous increase in the level of protein thiol groups and reduced glutathione. In addition, treatment with complexes increased the activity of the antioxidant defence system of cells.

Conclusions. The obtained results indicate that ORN-D-M complexes have a potential hepatoprotective effect in TAA-induced liver fibrosis. The complexes are able to effectively reduce the indicators of oxidative damage of biomolecules with a simultaneous increase in the activity of enzymes of the antioxidant system in TAA-induced fibrosis

Author Biographies

Tetiana Marchyshak, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143

Junior Researcher

Department of Enzymology of Protein Synthesis

Tetiana Yakovenko, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143

Leading Engineer

Department of Enzymology of Protein Synthesis

Zenoviy Tkachuk, Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine Akademika Zabolotnoho str., 150, Kyiv, Ukraine, 03143

PhD, Senior Researcher

Department of Enzymology of Protein Synthesis

References

  1. Aydin, M. M., Akcali, K. C. (2018). Liver fibrosis. The Turkish Journal of Gastroenterology, 29 (1), 14–21. doi: http://doi.org/10.5152/tjg.2018.17330
  2. Parola, M., Pinzani, M. (2019). Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Molecular Aspects of Medicine, 65, 37–55. doi: http://doi.org/10.1016/j.mam.2018.09.002
  3. Higashi, T., Friedman, S. L., Hoshida, Y. (2017). Hepatic stellate cells as key target in liver fibrosis. Advanced Drug Delivery Reviews, 121, 27–42. doi: http://doi.org/10.1016/j.addr.2017.05.007
  4. Luangmonkong, T., Suriguga, S., Mutsaers, H. A. M., Groothuis, G. M. M., Olinga, P., Boersema, M. (2018). Targeting Oxidative Stress for the Treatment of Liver Fibrosis. Reviews of Physiology, Biochemistry and Pharmacology, 175, 71–102. doi: http://doi.org/10.1007/112_2018_10
  5. Tacke, F. (2017). Targeting hepatic macrophages to treat liver diseases. Journal of Hepatology, 66 (6), 1300–1312. doi: http://doi.org/10.1016/j.jhep.2017.02.026
  6. Koyama, Y., Brenner, D. A. (2017). Liver inflammation and fibrosis. Journal of Clinical Investigation, 127 (1), 55–64. doi: http://doi.org/10.1172/jci88881
  7. Heymann, F., Tacke, F. (2016). Immunology in the liver – from homeostasis to disease. Nature Reviews Gastroenterology & Hepatology, 13 (2), 88–110. doi: http://doi.org/10.1038/nrgastro.2015.200
  8. Weiskirchen, R. (2016). Hepatoprotective and anti-fibrotic agents: It’s time to take the next step. Frontiers in Pharmacology, 6, 303. doi: http://doi.org/10.3389/fphar.2015.00303
  9. Feng, R., Yuan, X., Shao, C., Ding, H., Liebe, R., Weng, H.-L. (2018). Are we any closer to treating liver fibrosis (and if no, why not)? Journal of Digestive Diseases, 19 (3), 118–126. doi: http://doi.org/10.1111/1751-2980.12584
  10. Melnichuk, N., Semernikova, L., Tkachuk, Z. (2017). Complexes of Oligoribonucleotides with D-Mannitol Inhibit Hemagglutinin-Glycan Interaction and Suppress Influenza A Virus H1N1 (A/FM/1/47) Infectivity In Vitro. Pharmaceuticals (Basel, Switzerland), 10 (3), 71. doi: http://doi.org/10.3390/ph10030071
  11. Vivcharyk, M. M., Ilchenko, O. O., Levchenko, S. M., Tkachuk, Z. Y. (2016). Complexation of RNA with mannitol, its spectral characteristics and biological activity. Reports of the National Academy of Sciences of Ukraine, 10, 78–83. doi: http://doi.org/10.15407/dopovidi2016.10.078
  12. Shchodryi, V. B., Kachkovskyi, O. D., Slominskyi, Y. L., Shaudyk, Y. O., Tkachuk, Z. Y. (2017). Study of the interaction between mannitol and nucleosides using fluorescent probe. Reports of the National Academy of Sciences of Ukraine, 7, 85–90. doi: http://doi.org/10.15407/dopovidi2017.07.085
  13. Shchodryi, V. B., Kozlov, O. V., Rybenchuk, A. O., Boyko, V. V., Bortnitskiy, V. I. (2017). Study of products of the interaction of RNA with mannitol, by using the pyrolytic mass spectrometry method. Reports of the National Academy of Sciences of Ukraine, 2, 79–87. doi: http://doi.org/10.15407/dopovidi2017.02.079
  14. Frolov, V., Sotska, Ya., Oksana, K., Tkachuk, Z. (2012). Otsinka efektyvnosti nukleksu v likuvanni khvorykh na khronichnyi virusnyi hepatyt S. Ukrainskyi medychnyi almanakh, 10, 16–18.
  15. Toropchyn, V. (2011). Vplyv kombinatsii enerlivu ta nukleksa na pokaznyky systemy hlutationu u khvorykh na nealkoholnyi steatohepatyt na tli syndromu khronichnoi vtomy. Ukrainskyi morfolohichnyi almanakh, 9, 124–128.
  16. Marchyshak, T., Yakovenko, T., Shmarakov, I., Tkachuk, Z. (2018). The Potential Protective Effect of Oligoribonucleotides-d-Mannitol Complexes against Thioacetamide-Induced Hepatotoxicity in Mice. Pharmaceuticals, 11 (3), 77. doi: http://doi.org/10.3390/ph11030077
  17. Shmarakov, I. O., Marchyshak, Т. V., Borschovetska, V. L., Marchenko, M. M., Tkachuk, Z. Y. (2015). Hepatoprotective activity of exogenous RNA. The Ukrainian Biochemical Journal, 87 (4), 37–44. doi: http://doi.org/10.15407/ubj87.04.037
  18. Ohkawa, H., Ohishi, N., Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95 (2), 351–358. doi: http://doi.org/10.1016/0003-2697(79)90738-3
  19. Levine, R. L., Garland, D., Oliver, C. N., Stadtman, E. R. (1990). Determination of Carbonyl Content in Oxidatively Modified Proteins. Methods in Enzymology, 186, 464–478. doi: http://doi.org/10.1016/0076-6879(90)86141-h
  20. Murphy, M. E., Kehrer, J. P. (1989). Oxidation state of tissue thiol groups and content of protein carbonyl groups in chickens with inherited muscular dystrophy. Biochemical Journal, 260 (2), 359–364. doi: http://doi.org/10.1042/bj2600359
  21. Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82 (1), 70–77. doi: http://doi.org/10.1016/0003-9861(59)90090-6
  22. Razygraev, A. V. (2004). Metod opredeleniia glutationperoksidaznoi aktivnosti s ispolzovaniem peroksida vodoroda i 5,5’-ditiobis (2-nitrobenzoinoi kisloty). Kliniko-laboratornii konsilium, 4, 19–22.
  23. Borvinskaia, E., Smirnov, L. (2010). Nekotorye metodicheskie aspekty opredeleniia aktivnosti glutation-S-transferazy v tkaniakh ryb. Uchenye zapiski petrozavodskogo gosudarstvennogo universiteta, 6, 19–21.
  24. Lai, M., Afdhal, N. H. (2019). Liver Fibrosis Determination. Gastroenterology Clinics of North America, 48 (2), 281–289. doi: http://doi.org/10.1016/j.gtc.2019.02.002
  25. Iredale, J., Campana, L. (2017). Regression of Liver Fibrosis. Seminars in Liver Disease, 37 (1), 1–10. doi: http://doi.org/10.1055/s-0036-1597816
  26. Zhang, C.-Y., Yuan, W.-G., He, P., Lei, J.-H., Wang, C.-X. (2016). Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World Journal of Gastroenterology, 22 (48), 10512–10522. doi: http://doi.org/10.3748/wjg.v22.i48.10512
  27. Tkachuk, Z. Y., Tkachuk, V. V., Tkachuk, L. V. (2006). The study on membrane-stabilizing and anti-inflammatory actions of yeast RNA in vivo and in vitro. Biopolymers and Cell, 22 (2), 109–116. doi: http://doi.org/10.7124/bc.000723
  28. Torok, N. J. (2016). Dysregulation of redox pathways in liver fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 311 (4), 667–674. doi: http://doi.org/10.1152/ajpgi.00050.2016
  29. Xu, F., Liu, C., Zhou, D., Zhang, L. (2016). TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis. Journal of Histochemistry & Cytochemistry, 64 (3), 157–167. doi: http://doi.org/10.1369/0022155415627681
  30. Li, Z. L., Shi, Y., Le, G., Ding, Y., Zhao, Q. (2016). 24-week exposure to oxidized tyrosine induces hepatic fibrosis involving activation of the MAPK/TGF- β 1 signaling pathway in sprague-dawley rats model. Oxidative Medicine and Cellular Longevity, 4 (1), 1–12. doi: http://doi.org/10.1155/2016/3123294
  31. Kim, J.-Y., An, H.-J., Kim, W.-H., Gwon, M.-G., Gu, H., Park, Y.-Y., Park, K.-K. (2017). Anti-fibrotic Effects of Synthetic Oligodeoxynucleotide for TGF-β1 and Smad in an Animal Model of Liver Cirrhosis. Molecular Therapy – Nucleic Acids, 8, 250–263. doi: http://doi.org/10.1016/j.omtn.2017.06.022

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Published

2020-06-30

How to Cite

Marchyshak, T., Yakovenko, T., & Tkachuk, Z. (2020). Effect of oligoribonucleotides with D-mannitol complexes on oxidative stress indicators against thioacetamide-induced liver fibrosis. ScienceRise: Biological Science, (3 (24), 35–40. https://doi.org/10.15587/2519-8025.2020.214418

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Section

Biological Sciences