ANTIOXIDANT, METABOLIC AND ANTITUMOR ACTIVITY OF TRITERPENOIDS COMBINATION WITH CYTOSTATICS

  • OLGA VOROBYOVA Department of Pharmaceutical Chemistry, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia
  • ELIZAVETA GRUBOVA Department of Pharmaceutical Chemistry, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia
  • KSENIYA BELYAEVA Laboratory of Experimental Medicine, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia
  • ANNA SOLOVYEVA Laboratory of Experimental Medicine, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia https://orcid.org/0000-0001-6890-4530
  • NADEZHDA PLOTNIKOVA Medicine Institute, N. P. Ogarev Mordovian State University, Bolshevistskaya St. 68,430005 Saransk, Russia
  • OLGA DERYABINA Medicine Institute, N. P. Ogarev Mordovian State University, Bolshevistskaya St. 68,430005 Saransk, Russia
  • NINA MELNIKOVA Department of Pharmaceutical Chemistry, Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University”, Ministry of Health of the Russian Federation, Minin sq., 10/1, 603005 Nizhny Novgorod, Russia

Abstract

Objective: To study the effect of betulin derivatives combination with 5-fluorouracil or hydrazine sulfate on the ROS generation, the SOD and LDH activity using rat blood, as well as the effect of combination drugs on Ehrlich carcinoma in experiments on mice.


Methods: We used a chemiluminescence technique to study the ROS generation, and spectrophotometry to determine the MDA level and the SOD and LDH activity. The model of transplanted Ehrlich ascites carcinoma was investigated on mice using a cytological analysis of ascitic fluid cells according to Pappenheim`s method.


Results: In vitro experiments on rat blood at the doses of 2, 5 and 10 μg per ml revealed the dose-dependent effect of combination drugs on the antioxidant properties. In plasma, the ROS generation and the MDA level increased by 10-300% in comparison with control at the doses of 5 and 10 μg per ml only. Still, the SOD and LDH activity in general increased by 10-130% in comparison with control under the action of the studied combination drugs. The study on mice showed the effectiveness of a combination of triterpenoids and cytostatics in Ehrlich ascites carcinoma therapy. The state and behavior of the animals improved, the volume of ascites fluid decreased by 40-50% after treatment for 10 d.


Conclusion: The combination of betulin derivatives with cytostatics can be used as antitumor drugs in Ehrlich ascites carcinoma therapy that is due to metabolic plasticity, increased ROS generation in enhanced antioxidant enzyme protection.

Keywords: Ehrlich carcinoma, Betulin-3,28-diacetate, Betulonic acid, Hydrazine sulfate, 5-fluorouracil, Antioxidant properties

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VOROBYOVA, O., E. GRUBOVA, K. BELYAEVA, A. SOLOVYEVA, N. PLOTNIKOVA, O. DERYABINA, and N. MELNIKOVA. “ANTIOXIDANT, METABOLIC AND ANTITUMOR ACTIVITY OF TRITERPENOIDS COMBINATION WITH CYTOSTATICS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 12, no. 3, Jan. 2020, pp. 49-56, doi:10.22159/ijpps.2020v12i3.36608.
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