Hepatoprotective Effect of Xymedon and its Conjugate with L-ascorbic Acid during Poisoning of Mice with a Semilethal Dose of Paracetamol

Abstract

There is currently an urgent need to develop effective therapies aimed at preventing the consequences of drug-induced liver injury (DILI). In this context, our study focused on assessing the hepatoprotective effect of pyrimidine derivatives of xymedon (1,2-dihydro-4,6-dimethyl-1-(2- hydroxyethyl)-pyrimidin-2-one) and its conjugate with L-ascorbic acid in a mouse model of paracetamol (acetaminophen) poisoning. ICR (CD-1) mice were treated with a single oral LD50 dose of paracetamol (425 mg/kg), followed by intraperitoneal injections of various doses of the test compounds at various doses half an hour later. The animals` survival was monitored for 5 days. On the day 6, biochemical and histopathological evaluations of the effects of the test compounds were conducted. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were analyzed. Malondialdehyde (MDA) levels in blood and liver tissue were also determined. Xymedon attenuated the toxic effects of paracetamol on the liver, improving animal survival and enhancing the macro- and micro-structure of the liver, normalizing the biochemical indicator of liver condition ALT and the serum marker of oxidative stress MDA. The conjugate of xymedon with L-ascorbic acid exhibited a more pronounced hepatoprotective effect compared to the native xymedon molecule.