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

Alexandra B VyshtakalyukAndrey A ParfenovLilya F GumarovaLeyla R KhasanshinaGrigory P BelyaevNail G NazarovDarya A KondrashinaIrina V GalyametdinovaVyacheslav E SemenovVladimir V Zobov
Published in: Journal of biochemical and molecular toxicology (2020)
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.
Keyphrases
  • endothelial cells
  • oxidative stress
  • induced apoptosis
  • cancer therapy
  • insulin resistance
  • drug delivery
  • cell death
  • pluripotent stem cells