Antifibrotic Effect of Pyrimidine Derivatives of Xymedon and Its Conjugate with L-Ascorbic Acid

G. Belyaev, A. Vyshtakalyuk, A. Parfenov, I. Galyametdinova, V. Semenov, V. Zobov
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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.
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Xymedon嘧啶衍生物及其与l -抗坏血酸缀合物的抗纤维化作用
本文考虑了药物Xymedon的嘧啶衍生物(化合物(I))及其与l -抗坏血酸(化合物(II))的结合物在实验性纤维化大鼠模型中的抗纤维化特性。实验性纤维化Wistar大鼠给予四氯化碳(5%油溶液,0.2 mL/kg,口服,每周2次)与乙醇(5%饮用水溶液,自由获取)联合抗化合物(I)和(II),两者都是预防性给药。Van Gieson染色法检测肝脏纤维化改变。通过血清生化指标评价所研究化合物对大鼠肝脏及临床状况的影响。与对照组相比,化合物(I)和(II)处理大鼠的纤维化区域数量减少了三倍,改善了肝脏脂肪变性和坏死,并改善了血液生化参数(ALT, AST和LDH)。有趣的是,化合物(II)的效果更明显。因此,Xymedon的嘧啶衍生物及其与l -抗坏血酸的结合物在我们的实验性纤维化大鼠模型中显示出抗纤维化作用。
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0.70
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审稿时长
17 weeks
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