Antifibrotic effect of pyrimidine derivatives of Xymedon and its conjugate with L-ascorbic acid

G.P. Belyaev^*, A.B. Vyshtakalyuk^**, A.A. Parfenov^***, I.V. Galyametdinova^****,

V.E. Semenov^*****, V.V. Zobov^******

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 Russia

E-mail: ^*gregoir4@gmail.com, ^**alex.vysh@mail.ru, ^***aimt66@gmail.com, 

^****iragal2009@yahoo.com, ^*****sve@iopc.ru, ^******vz30608@mail.ru

Received June 29, 2022; Accepted October 7, 2022

ORIGINAL ARTICLE

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DOI: 10.26907/2542-064X.2023.2.175-189

For citation: Belyaev G.P., Vyshtakalyuk A.B., Parfenov A.A., Galyametdinova I.V., Semenov V.E., Zobov V.V. Antifibrotic effect of pyrimidine derivatives of Xymedon and its conjugate with L-ascorbic acid. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2023, vol. 165, no. 2, pp. 175–189. doi: 10.26907/2542-064X.2023.2.175-189. (In Russian) 

Abstract

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.

Keywords: fibrosis, antifibrotic effect, collagen, Xymedon, carbon tetrachloride

Acknowledgements. This study was performed under the state assignment to the FRC Kazan Scientific Center, Russian Academy of Sciences.

Figure Captions

Fig. 1. Structural formulas of the studied compounds. 1 – Xymedon (compound (I)), 2 – conjugate of Xymedon with L-ascorbic acid (compound (II)).

Fig. 2. Effect of compounds (I) and (II) on the rat liver mass ratio. 1 – intact control group, 2 – control group, 3 – compound (I) group, 4 – compound (II) group. * – differences with the intact group are reliable, p < 0.05; # – differences with the control group are reliable, p < 0.05.

Fig. 3. Effect of compounds (I) and (II) on the cell damage markers. A – aspartate aminotransferase (AST) activity, B – alanine aminotransferase (ALT) activity, C – lactate dehydrogenase (LDH) activity. 1 – intact control group, 2 – control group, 3 – compound (I) group, 4 – compound (II) group. * – differences with the intact control group are reliable, p < 0.05; # – differences with the control group are reliable, p < 0.05.

Fig. 4. Effect of compounds (I) and (II) on the liver tissue morphology, hematoxylin and eosin staining, magnification 100x and 200x.

Fig. 5. Effect of compounds (I) and (II) on the development of collagen fibers (red) in the liver tissue, Van Gieson’s staining, magnification 100x and 200x.

Fig. 6. Effect of compounds (I) and (II) on the development of collagen fibers (red) in the liver tissue, Van Gieson’s staining without Weigert’s hematoxylin to contrast collagen staining, magnification 40x.

Fig. 7. Effect of compounds (I) and (II) on the percentage of collagen area in the rat liver tissue. 1 – intact control group, 2 – control group, 3 – compound (I) group, 4 – compound (II) group. * – differences with the intact control group are reliable, p < 0.0085; # – differences with the control group are reliable, p < 0.0085.

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