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Hepatoprotective and antioxidant effects of oligoribonucleotides-D-mannitol complexes against thioacetamide-induced liver fibrosis
* , , , *
1  Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine

Published: 03 November 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session ECMC-4

Aim: Hepatic fibrosis is a common consequence of chronic liver injury caused by a variety of etiological factors. It is associated with inflammation, oxidative stress, necrosis and ends with cirrhosis, liver cancer, or liver failure. Oligoribonucleotides-D-mannitol complexes (ORNs-D-M) display a vast spectrum of biological effects, including cellular metabolism stimulation with activation of endogenous synthesis of regulatory proteins, stimulation of reparation processes. Therefore, the aim of this study was to investigate the protective effect of the ORNs-D-M on liver fibrosis.

Materials and methods: Mice received thioacetamide (TAA) (200 mg/kg, intraperitoneal) thrice weekly, for 8 successive weeks to induce liver fibrosis. The ОRNs-D-M (200 mg/kg, per os) was administered orally during TAA intoxication. Body weights and mortality mice were assessed during the experiment. At the end of the experiment, oxidative stress, inflammatory and profibrogenic markers were evaluated.

Results: The results of the research showed that treatment with the ORNs-D-M attenuated TAA-induced liver fibrosis in mice. The ORNs-D-M prevented TAA oxidative stress. The ORNs-D-M decreased TBA-reactive substances, carbonyl derivatives levels and myeloperoxidase activity by 60.6, 35 and 52% respectively in comparison to control thioacetamide in the liver cells. In addition, these complexes increased protein and non-protein thiol groups levels, and glutathione-S-transferase and glutathione peroxidase activities compared to the TAA-treated mice. During TAA-induced liver fibrosis, it was investigated that the ORNs-D-M reduced the expression mRNA level of pro-inflammatory (IL-6, TNF-α) genes by 40 and 56 % respectively, compared to the mice with TAA. Furthermore, the ORNs-D-M suppressed the HSCs/myofibroblasts activation by reduced expression of markers α-SMA, COL-1, and TGF-β1 in the liver.

Conclusion: The ORNs-D-M could ameliorate the effects of TAA-induced liver fibrosis in mice by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and profibrotic markers.

Keywords: Oligoribonucleotides-D-mannitol complexes; liver fibrosis; thioacetamide.