uzakuescУченые записки Казанского университета. Серия Естественные наукиUchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki2542-064X2500-218XKazan (Volga Region) Federal University10.26907/2542-064X.2025.2.276-296uzakuesc-347Research ArticleСтатьиКсимедон и его конъюгат с L-аскорбиновой кислотой при лечении экспериментально вызванного фиброза печени крысXymedon and its conjugate with L-ascorbic acid for treating experimentally induced liver fibrosis in ratshttps://orcid.org/0000-0003-3157-3402БеляевГ. П.BelyaevG. P.

Григорий Павлович Беляев - аспирант, младший научный сотрудник лаборатории нейрофизиологии.

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gregoir4@gmail.comhttps://orcid.org/0000-0003-2152-2249ВыштакалюкА. Б.VyshtakalyukA. B.

Александра Борисовна Выштакалюк - доктор биологических наук, старший научный сотрудник лаборатории химико-биологических исследований.

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alex.vysh@mail.ruhttps://orcid.org/0000-0001-5650-1910ПарфеновА. А.ParfenovA. A.

Андрей Анатольевич Парфенов - кандидат биологических наук, младший научный сотрудник лаборатории химико-биологических исследований.

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aimt66@gmail.comГаляметдиноваИ. В.GalyametdinovaI. V.

Ирина Владимировна Галяметдинова - кандидат химических наук, научный сотрудник лаборатории химии нуклеотидных оснований.

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iragal2009@yahoo.comhttps://orcid.org/0000-0001-8350-2433СеменовВ. Э.SemenovV. E.

Вячеслав Энгельсович Семенов - доктор химических наук, профессор, главный научный сотрудник, заведующий лабораторией химии нуклеотидных оснований.

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sve@iopc.ruhttps://orcid.org/0000-0001-6910-3540ЗобовВ. В.ZobovV. V.

Владимир Васильевич Зобов - доктор биологических наук, профессор, главный научный сотрудник, заведующий лабораторией химико-биологических исследований.

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vz30608@mail.ruИнститут органической и физической химии им. А.Е. Арбузова – обособленное структурное подразделение ФИЦ КазНЦ РАНРоссияArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of the Russian Academy of SciencesRussian Federation2025110620251672276296Copyright © Беляев Г.П., Выштакалюк А.Б., Парфенов А.А., Галяметдинова И.В., Семенов В.Э., Зобов В.В., 20252025Беляев Г.П., Выштакалюк А.Б., Парфенов А.А., Галяметдинова И.В., Семенов В.Э., Зобов В.В.Belyaev G.P., Vyshtakalyuk A.B., Parfenov A.A., Galyametdinova I.V., Semenov V.E., Zobov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://uzakuesc.elpub.ru/jour/article/view/347

Работа посвящена оценке антифиброзных свойств производного пиримидина ксимедона (1,2-дигидро-4,6-диметил-1-(2-гидроксиэтил)-пиримидин-2-она) и его конъюгата с L-аскорбиновой кислотой при лечении экспериментального фиброза печени крыс. Фиброз печени моделировали у самок крыс линии Wistar путем перорального введения 5 %-ного масляного раствора CCl4 в дозе 2 мл/кг два раза в неделю и 5 %-ного этанола через поилки при постоянном доступе на протяжении 8 недель. Затем введение токсикантов отменяли и проводили лечение фиброза ксимедоном в дозе 0.24 мг/кг или его конъюгатом с L-аскорбиновой кислотой в эквимолярной дозе 0.5 мг/кг в течение двух или четырех недель. Затем, используя методы окраски гематоксилин–эозином и по Ван-Гизону, проводили гистологическую оценку ткани печени, а также биохимических сывороточных показателей состояния печени. Кроме того, с помощью мультиплексного иммуноферментного анализа MagPix рассмотрен цитокиновый профиль печени и сыворотки крови, а также выявлен уровень циклооксигеназы-2 (ЦОГ-2) в печени по данным вестерн-блот-анализа. Показано, что лечение фиброза печени конъюгатом ксимедона с L-аскорбиновой кислотой в течение двух недель способствует более выраженному разрешению фиброза за счет уменьшения площади коллагеновых волокон в ткани печени крыс. Кроме того, конъюгат ксимедона с L-аскорбиновой кислотой приводит к нормализации биохимических показателей крови, маркеров цитокинового профиля, а также уровня ЦОГ-2 по сравнению с группой, получавшей только ксимедон, и контрольной группой.

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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The authors declare that there are no conflicts of interest present.