Marchyshak T. Hepatoprotective effect of oligoribonucleotide complex with D-mannitol in thioacetamide-induced hepatotoxicity in experimental animal models

The dissertation is devoted to the study of the hepatoprotective effect of the complex of oligoribonucleotides with D-mannitol in thioacetamide-induced hepatotoxicity in experimental animal models. For the first time, it has been shown, that the use of the drug ORN-D-M reduces damage to the liver parenchyma and the recruitment of immune cells to the site of inflammation. It was determined that the ORH-D-M complex leads to inhibition of TAA-induced free radical damage of mouse hepatocyte biomolecules by reducing the generation of oxidative degradation products and increasing the activity of enzymes and the content of non-enzymatic components of the antioxidant defense system. For the first time, it has been shown, that the ORN-D-M at a dose of 200 mg/kg body weight of animals reduces the level of relative expression of universal transcription factor Nfkb1, which inhibits the induction of cytokines, in particular, interleukin 6 (Il6) and tumor necrosis factor α (Tnfα) under acute hepatotoxicity. A low level of relative expression of the smooth muscle α-actin gene (Acta 2) was detected when using the drug for therapeutic purposes. It is shown that ORH-D-M reduces the profiles of relative expression of transforming growth factor β1 (Tgfβ1) and collagen A-1 (Col1a1) genes in acute toxic liver damage. It was found that the drug does not change the profiles of relative expression of growth factors - hepatocyte growth factor (Hgf), transforming growth factor α (Tgfα), and epidermal growth factor (Egf), which are involved in regenerative processes in acute toxic liver disease. For the first time, it has been shown, that the detected hepatoprotective effect of the ORH-D-M complex in the model of acute hepatotoxicity persists in chronic toxic liver damage. It was found that long-term treatment with the drug effectively reduces the elevated levels of relative expression of genes Nfkb1, Nfkbia, proinflammatory cytokines (Il6, Tnfα), and profibrotic genes (Tgfβ1, Col1a1, Acta 2) in the liver parenchyma, which leads to a decrease in extracellular proteins under chronic liver damage.