Conjugate of pyrimidine derivative, the drug xymedon with succinic acid protects liver cells

Abstract

The aim of the study was to investigate the hepatoprotective properties of the conjugate of the xymedon drug substance with succinic acid (1a). The study presents an in vitro comparative evaluation of the cytotoxicity and cytoprotective properties of 1a and succinic acid on a cell line of normal human hepatocytes Chang Liver, and in vivo investigation of the ability of 1a to restore liver from the toxic damage caused by CCl4 in Wistar rats. It was shown that the cytotoxicity of 1a was 19.9 ± 0.8 mmol/L, and that of succinic acid was 14.1 ± 0.2 mmol/L. Against the background of d‐galactosamine exposure, the cytoprotective effect of 1a was found to be superior to that of succinic acid. It was shown that 1a caused a significant reduction in necrotic and steatosis changes in the liver and restoration of biochemical markers of cytolysis, as well as bilirubin metabolism and synthetic liver function.

Untitled

“…Histological Studies: Histological processingpreparation of paraffin sections, staining with Garris hematoxylin (BioVitrum, Russia), alcohol eosin (BioVitrum, Russia) were performed according to standard protocols described in more detail in our previous works [3][4][5][6][7] . Frozen sections were also prepared and stained with Sudan 4 (BioVitrum, Russia) according to standard protocols.…”

“…Earlier data have shown that conjugation of Xymedon with some bioactive acids leads to an increase in the protective effect of the Xymedon molecule itself [3][4][5] . As a result of exploratory studies, Xymedon conjugate with L-ascorbic acid, among other studied conjugates, has a more pronounced and stable hepatoprotective effect.…”

Studies on the Changes of Fermentation Metabolites and the Protective Effect of Fermented Edible Grass on Stress Injury Induced by Acetaminophen in HepG2 Cells

“…Succinic acid is able to activate the succinate receptor 1 (SUCNR1 or GPR91) in the liver and facilitate reparative processes in the liver [46]. Compared with the model group, the fermented edible grass group showed an increased level of intracellular succinic acid, indicating that fermented edible grass could reduce cell damage by providing succinic acid.…”

Anti-Apoptosis Mechanism of the Hepatoprotective Effect of Pyrimidine Derivatives in In Vivo Studies

“…Гистологическую проводку, приготовление парафиновых срезов, окрашивание гематоксилином Гарриса (BioVitrum, Россия), спиртовым эозином (BioVitrum, Россия) осуществляли по стандартным протоколам, более подробно описанным в работах [4][5][6][7][8][9]. Приготовление замороженных срезов и окрашивание их суданом 4 (BioVitrum, Россия) также выполняли по стандартным протоколам.…”

“…Несвоевременно начатое лечение легких форм патологий печени, вызванных действием гепатотоксических веществ, может привести к более серьезным, вплоть до некротических повреждений [1]. Объектом настоящего исследования были лекарственный препарат на основе производного Ранее были получены данные, которые показали, что конъюгирование Ксимедона с некоторыми биологически активными кислотами приводит к усилению протекторного действия самой молекулы Ксимедона [3][4][5][6][7][8][9].…”