ANTIOXIDANT, METABOLIC AND ANTITUMOR ACTIVITY OF TRITERPENOIDS COMBINATION WITH CYTOSTATICS

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

Betulin-3,28-diphosphate as a Component of Combination Cytostatic Drugs for the Treatment of Ehrlich Ascites Carcinoma In Vitro and In Vivo Experiments

The activity of betulin-3,28-diphosphate (BDP) in combination with the cytostatics such as 5-fluorouracil (5-FU) and hydrazine sulfate (HS) was demonstrated by using the transplanted Ehrlich ascites carcinoma (EAC) in mice. The dose-dependent effect of combination drugs BDP + HS and BDP + 5-FU was revealed by in vitro experiments on rats. The synergetic effect of HS and BDP on oxidative stress and energy metabolism was established. The malonic dialdehyde (MDA) level both in plasma and erythrocytes decreased by 87 ± 2%, and the superoxide dismutase (SOD) activity increased by 105 ± 7% in comparison with the control. The combination of BDP + HS promoted the increase of lactate dehydrogenase (LDH) activity in the reverse reaction by 195 ± 21% compared to the control. The combination drug of 5-FU with BDP caused the synergetic decrease of the lipid peroxidation (LPO) intensity estimated by the MDA level decrease up to 14 ± 4% compared to pure compounds. Betulin-3,28-diphosphate in combination with cytostatics for EAC treatment improved the animal health status, as well as decreased the cytostatics dose that can be used in palliative therapy

Simultaneous Determination of Steroidal Alkaloids and Polyphenol Group from Eight Varieties of Siberian <i>Solanum tuberosum</i> L. through Tandem Mass Spectrometry

The purpose of this work was a comparative metabolomic study of extracts of from Siberian breeds of the Solanum tuberosum L.: Tuleevsky, Kuznechanka, Memory of Antoshkina, Tomichka, Hybrid 15/F-2-13, Hybrid 22103-10, Hybrid 17-5/6-11, and Sinilga from the collection of Siberian Federal Scientific Centre of Agrobiotechnology of the Russian Academy of Sciences. HPLC was used in combination with ion trap to identify target analytes in extracts of tuber part of a potato. The results showed the presence of 87 target analytes corresponding to S. tuberosum. In addition to the reported metabolites, a number of metabolites were newly annotated in S. tuberosum. There were essential amino acid L-Tryptophan, L-glutamate, L-lysine, Nordenine; flavones Ampelopsin; Chrysoeriol, Diosmetin, Diosmin, Myricetin; flavanones Naringenin and Eriodictyol-7-O-glucoside; dihydrochalcone Phlorizin; oligomeric proanthocyanidin (Epi)afzelechin-(epi)afzelechin; Shikimic acid; Hydroxyphenyllactic acid; Fraxidin; Myristoleic acid; flavan-3-ols Epicatechin, Gallocatechin, Gibberellic acid, etc

Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax