Xymedon and its conjugate with L-ascorbic acid for treating experimentally induced liver fibrosis in rats

This study evaluates the antifibrotic properties of Xymedon, a pyrimidine derivative (1,2-dihydro-4,6-dimethyl-1-(2-hydroxyethyl)-pyrimidin-2-one), and its conjugate with L-ascorbic acid in a rat model of experimental liver fibrosis. Liver fibrosis was induced in female Wistar rats by oral administration of 5 % oil solution of CCl₄ at a dose of 2 mL/kg twice weekly and 5 % ethanol in drinking water with constant access for 8 weeks. After discontinuing the administration of toxicants, the rats were treated with Xymedon at a dose of 0.24 mg/kg and its conjugate with L-ascorbic acid at an equimolar dose of 0.5 mg/kg for 2 or 4 weeks. Histological evaluation of the liver tissue was performed using hematoxylin– eosin and Van Gieson’s staining. Serum biochemical indicators of liver function were determined. Additionally, the cytokine profile of the liver tissue and serum was examined using the MagPix multiplex immunoassay, and liver COX-2 levels were measured by western blot analysis. The findings demonstrate that the treatment with the conjugate of Xymedon with L-ascorbic acid for 2 weeks significantly promoted fibrosis resolution by reducing the area of collagen fibers in the liver tissue of rats. This treatment also resulted in a more pronounced normalization of blood biochemical parameters, cytokine profile markers, and COX-2 levels compared to Xymedon alone and the untreated control group.

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