Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies
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 o...
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Kazan Federal University
2022-06-01
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| Series: | Учёные записки Казанского университета: Серия Естественные науки |
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| Online Access: | https://kpfu.ru/uz-eng-ns-2022-2-4.html |
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| author | A.A. Parfenov A.B. Vyshtakalyuk I.V. Galyametdinova V.E. Semenov V.V. Zobov |
| author_facet | A.A. Parfenov A.B. Vyshtakalyuk I.V. Galyametdinova V.E. Semenov V.V. Zobov |
| author_sort | A.A. Parfenov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-395171a9f416480ba5097934400d232e |
| institution | Kabale University |
| issn | 2542-064X 2500-218X |
| language | English |
| publishDate | 2022-06-01 |
| publisher | Kazan Federal University |
| record_format | Article |
| series | Учёные записки Казанского университета: Серия Естественные науки |
| spelling | doaj-art-395171a9f416480ba5097934400d232e2025-01-02T05:48:09ZengKazan Federal UniversityУчёные записки Казанского университета: Серия Естественные науки2542-064X2500-218X2022-06-01164223124810.26907/2542-064X.2022.2.231-248Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studiesA.A. Parfenov0A.B. Vyshtakalyuk1I.V. Galyametdinova2V.E. Semenov3V.V. Zobov4Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 Russia; Kazan Federal University, Kazan, 420008 RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 Russia; Kazan National Research Technological University, Kazan, 420015 RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420088 Russia; Kazan Federal University, Kazan, 420008 RussiaThis 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.https://kpfu.ru/uz-eng-ns-2022-2-4.htmlpyrimidine derivativesxymedonapoptosiscarbon tetrachloridetoxic liver damage |
| spellingShingle | A.A. Parfenov A.B. Vyshtakalyuk I.V. Galyametdinova V.E. Semenov V.V. Zobov Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies Учёные записки Казанского университета: Серия Естественные науки pyrimidine derivatives xymedon apoptosis carbon tetrachloride toxic liver damage |
| title | Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| title_full | Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| title_fullStr | Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| title_full_unstemmed | Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| title_short | Anti-apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| title_sort | anti apoptosis mechanism of the hepatoprotective effect of pyrimidine derivatives in in vivo studies |
| topic | pyrimidine derivatives xymedon apoptosis carbon tetrachloride toxic liver damage |
| url | https://kpfu.ru/uz-eng-ns-2022-2-4.html |
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