Therapeutic application of oligonucleotides is a leading trend in correction of metabolic disorders and related pathologies and is perceived as a unique foundation of innovative biomedicine. Oligoribonucleotides-D-mannitol complexes (ORNs-D-mannitol) display a vast spectrum of biological effects, including cellular metabolism stimulation with activation of endogenous synthesis of regulatory proteins, stimulation of reparation processes. The high biological activity of these complexes promotes the study of the hepatoprotective activity in acute hepatotoxicity. The objective of this research was to study hepatoprotective effects of the ORNs-D-mannitol under thioacetamide liver toxicity in mice. It was demonstrated, that a dose of 200 mg/kg of these complexes decrease lesions and inflammatory infiltration of liver parenchyma under thioacetamide-induced hepatotoxicity. The ORNs-D-mannitol attenuated thioacetamide-induced free radical damage of hepatic biopolymers that is expressed in reduction of TBA-reactive products, carbonyl derivatives and in recovery of protein thiol groups, reduced glutathione. During thioacetamide toxicity it was observed that the ORNs-D-mannitol reduced the expression mRNA level of proinflammatory (Il6, Tgf α) and profibrotic (Col1A1, αSma, Tgfβ1) genes by 65, 80, 75, 77 and 87 % respectively in comparison to control thioacetamide in the liver cells.
Thus, the results of this work demonstrate that the ORNs-D-mannitol have the hepatoprotective effect during acute liver injury. These complexes attenuate thioacetamide-induced free-radical damage of liver biopolymers and modulate the expression of some genes, which are involved in the development of liver damage at the thioacetamide toxicity.