Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies

Abstract

This study investigates the effect of pyrimidine derivatives (Xymedon and its conjugate with L-ascorbic acid, both exhibiting hepatoprotective activity) on the apoptosis of rat liver cells against the background of exposure to carbon tetrachloride as a hepatotoxic agent. The characteristic markers of apoptosis affected by the considered compounds were identified. Modern multiplex analysis of the early apoptosis markers Akt, BAD, BCL-2, p53, Active Caspase-8, and Active Caspase-9 in rat liver homogenates using the MagPix system (MerkMillipore, USA) was selected as the main research method. The results obtained show that Xymedon and its derivative with L-ascorbic acid exert an anti-apoptotic effect by causing a significant decrease in the number of the early apoptosis markers BAD and Active Caspase-9. The derivative with L-ascorbic acid was also found to reduce p53 expression. Moreover, it was revealed that the studied pyrimidine derivatives normalize the biochemical markers of liver damage (transaminases, alkaline phosphatase, bilirubin, total protein, and albumin) and increase the level of glucose in the blood serum of rats against the background of acute toxic damage to the liver by carbon tetrachloride. Our findings are of the utmost theoretical and practical relevance for better understanding the mechanisms of the action of pyrimidine derivatives and for developing a highly effective hepatoprotective drug.

Keywords

• pyrimidine derivatives
• xymedon
• apoptosis
• carbon tetrachloride
• toxic liver damage