This study investigates the effect of pyrimidine derivatives (Xymedon and its conjugate with L-ascorbic acid, both exhibiting hepatoprotective activity) on the apoptosis of rat liver cells against the background of exposure to carbon tetrachloride as a hepatotoxic agent. The characteristic markers of apoptosis affected by the considered compounds were identified. Modern multiplex analysis of the early apoptosis markers Akt, BAD, BCL-2, p53, Active Caspase-8, and Active Caspase-9 in rat liver homogenates using the MagPix
This article considers the antifibrotic properties of pyrimidine derivatives of the drug Xymedon (compound (I)) and its conjugate with L-ascorbic acid (compound (II)) in an experimental rat model of fibrosis with a preventive administration scheme. Experimental fibrosis was induced in Wistar rats given carbon tetrachloride (5% oil solution, 0.2 mL/kg orally twice a week) in combination with ethanol (5% solution in drinking water, free access) against compounds (I) and (II), both administered preventively. Fibrotic changes in the liver were detected by Van Gieson’s staining. The effects of the studied compounds on the liver and clinical condition of rats were evaluated through serum biochemical parameters. The treatment of rats with compounds (I) and (II) reduced the number of fibrotic areas threefold, ameliorated hepatic steatosis and necrosis as compared to the control group, and improved blood biochemical parameters (ALT, AST, and LDH). Interestingly, compound (II) had a more pronounced effect. Therefore, pyrimidine derivatives of Xymedon and its conjugate with L-ascorbic acid showed an antifibrotic effect in our experimental rat model of fibrosis.
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