Influence of oligoribonucleotides-D-mannitol complexes on the expression of genes under acute thioacetamide-induced hepatotoxicity

TitleInfluence of oligoribonucleotides-D-mannitol complexes on the expression of genes under acute thioacetamide-induced hepatotoxicity
Publication TypeJournal Article
Year of Publication2018
AuthorsMarchyshak, TV, Yakovenko, TG, Tkachuk, ZYu.
Abbreviated Key TitleDopov. Nac. akad. nauk Ukr.
Date Published7/2018

The effect of oligoribonucleotides-D-mannitol complexes on the expression of IL-6, TNF-α, TGF-β1, and COL1A1 mRNA genes under acute hepatotoxicity has been investigated. It is shown that the administration of ORNs—D-M complexes results in the downregulation of genes encoding pro-inflammatory cytokines, including the tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), profibrogenic cytokine TGF-β1, as well as the predominant protein of hepatic extracellular matrix — collagen I (COL1A1). The obtained results indicate that ORN—D-M complexes can modulate the expression of pro-inflammatory and profibrogenic genes involved in the development of the pathological process.

Keywordsexpression of mRNA genes, ORN—D-M complexes, thioacetamide-induced hepatotoxicity
  1. Pandit, A., Sachdeva, T. & Bafna, P. (2012). Drug-induced hepatotoxicity: A review. J. App. Pharm. Sci., 2, Iss. 5, pp. 233-243. doi:
  2. Luo, M., Dong, L., Li, J., Wang, Y. & Shang, B. (2015). Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats. Int. J. Clin. Exp. Pathol. 8, No. 8, pp. 8990-8996.
  3. Hermenean, A., Mariasiu, T., Navarro-González, I., Vegara-Meseguer, J., Miuţescu E., Chakraborty, S. & Pérez-Sánchez, H. (2017). Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling. Exp. Ther. Med., 13, No. 5, pp. 1671-1680. doi:
  4. Friedman, S. L. (2000). Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem., 275, No. 4, pp. 2247-2250. doi:
  5. Higashi, T., Friedman, S. L. & Hoshida, Y. (2017). Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev., 121, pp. 27-42. doi:
  6. Ponnappa, B., Israel, Y., Aini, M., Zhou, F., Russ, R.,Cao, Q., Hu, Y. & Rubin, R. (2005). Inhibition of tumor necrosis factor alpha secretion and prevention of liver injury in ethanol-fed rats by antisense oligonucleotides. Biochem. Pharmacol., 69, No. 4, pp. 569-577. doi:
  7. Doh, K., Jung, H., Moon, I., Kang, H., Park, J. & Park, J. (2008). Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-β1. Int. J. Mol. Med., 21, No. 1, pp. 33-39. doi:
  8. Shapovalova, I. A. (2011). Influence of nucleinas and α-tokopherol combination on liver functional tests of the patients with chronic toxic hepatitis, combined with a chronic uncalculosis cholecystitis on background obesity. Ukr. Morp. Alm., 9, No. 1, pp. 155-158 (in Ukrainian).
  9. Pinzani, M. & Macias-Barragan, J. (2010). Update on the pathophysiology of liver fibrosis. Expert. Rev. Gastroenterol. Hepatol., 4, No. 4, pp. 459-472. doi:
  10. Wang, F., Liu, S., Du, T., Chen, H., Li, Z. &Yan, J. (2014). NF-κB inhibition alleviates carbon tetrachlorideinduced liver fibrosis via suppression of activated hepatic stellate cells. Exp. Ther. Med., 8, No. 1, pp. 95-99. doi:
  11. Friedman, S. L. (2008). Mechanisms of hepatic fibrogenesis. Gastroenterology, 134, No. 6, pp. 1655-1669. doi:
  12. Wang, T., Wu, D., Li, P., Zhang, K., Tao, S., Li, Z. & Li, J. (2017). Effects of Taohongsiwu decoction on the expression of α-SMA and TGF-β1 mRNA in the liver tissues of a rat model of hepatic cirrhosis. Exp. Ther. Med., 14, No. 2, pp. 1074-1080. doi:
  13. Friedman, S. L. (2008). Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev., 88, No. 1, pp. 125-172. doi: