This study investigated the potential hepatoprotective effect of oligoribonucleotides-d-mannitol complexes (ORNs-d-M) against thioacetamide (TAA)-induced hepatotoxicity in mice. The hepatoprotective activity of ORNs-d-M was evaluated in thioacetamide (TAA)-treated C57BL/6J. Results indicate that treatment with ORNs-d-M displayed a protective effect at the TAA-induced liver injury. Treatment with ORNs-d-M, starting at 0 h after the administration of TAA, decreased TAA-elevated serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT). Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx), and levels of glutathione (GSH), were enhanced with ORNs-d-M administration, while the hepatic oxidative biomarkers (TBA-reactive substances, protein carbonyl derivatives, protein-SH group) and myeloperoxidase (MPO) activity were reduced. Furthermore, genetic analysis has shown that the ORNs-d-M decreases the expression of mRNA pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), profibrogenic cytokine-transforming growth factor β1 (TGF-β1), as well as the principal protein of the extracellular matrix—collagen I. The present study demonstrates that ORNs-d-M exerts a protective effect against TAA-induced liver injury, which may be associated with its anti-inflammatory effects, inhibition of overexpression of mRNA cytokines, and direct effects on the metabolism of the toxin.
hepatoprotective activity of nuclex, a pharmaceutical composed of low-molecular yeast rna, was investigated during acute and chronic thioacetamide-induced hepatotoxicity. It is demonstrated, that nuclex administration at a dose of 200 mg/kg during acute and chronic liver injury produces hepatoprotective effect, which is associated with decrease in liver parenchyma lesions and in its inflammatory infiltration. nuclex application attenuates thioacetamide-induced free radical damage of hepatic biopolymers, expressed in the reduction of tBa-reactive products, carbonyl derivatives, and recovery of protein thiol groups and reduced glutathione levels.
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 TAAinduced fibrosis
Hepatic fibrosis is a reversible wound-healing response of the liver to a variety of etiological factors. The cascade of reactions that leads to liver fibrosis includes inflammation, oxidative stress, and activation of hepatic stellate cell. Activated stellate cells overexpress the components of the extracellular matrix, including fibril-forming type I and III collagens, elastin, and glycoproteins. This overexpression leads to the deposition of collagen contributing to the development of liver fibrosis. Oligoribonucleotides-D-mannitol complexes (ORNs-D-M) display a vast spectrum of biological effects, ORNs-D-M has been previously reported to exhibit antiinflammatory, membrane-stabilizing and antioxidant activities under acute hepatotoxicity. However, there is no previous study investigated the efficacy of ORNs-D-M on hepatic fibrosis. Therefore, the aim of this study was to investigate the protective effect of the ORNs-D-mannitol on liver fibrosis. The results of the research showed that treatment with the ORNs-D-mannitol attenuated TAAinduced liver fibrosis that is expressed in reduction of TBA-reactive substances (TBARS), carbonyl derivatives, myeloperoxidase (MPO) activity and in recovery of protein thiol groups, reduced glutathione, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. During TAA-induced liver fibrosis was investigated that the ORNs-D-mannitol reduced the expression mRNA level of pro-inflammatory genes. Furthermore, the ORNs-D-mannitol suppress the HSCs/myofibroblasts activation by reduced expression of α-SMA, COL-1, and TGF-β1 markers in the liver.
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