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

Olga Vorobyova,Kseniya Belyaeva,Nadezhda Plotnikova,Darina Malygina,Nina Melnikova,Anna Solovyeva,Olga Deryabina

doi:10.3390/scipharm86020017

Olga Vorobyova, Kseniya Belyaeva + Show 5 more

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https://doi.org/10.3390/scipharm86020017

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Abstract

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.

Highlights

Patients’ quality of life is an important issue in oncology in parallel with optimal pharmacotherapy by cytostatics, radiation therapy, and/or surgical interventions
The combination drug of 5-FU with BDP caused the synergetic decrease of the lipid peroxidation (LPO) intensity estimated by the malonic dialdehyde (MDA) level decrease up to 14 ± 4% compared to pure compounds
The present study evaluated the effect of BDP and its combination with cytostatics using the biochemical parameters of nontumor rat blood to obtain a response to the biological system

Summary

Introduction

Patients’ quality of life is an important issue in oncology in parallel with optimal pharmacotherapy by cytostatics, radiation therapy, and/or surgical interventions. The toxic effects of cytostatics are largely determined by their bioavailability, which depends on the hydrophilic-lipophilic ratio and solubility of drugs. Highly water-soluble substances have severe systemic toxic effects. The modern trend of pharmacotherapy is to use well-proven drugs in new dosage forms or new methods of administration, such as selective delivery when the dose of cytostatics can be dramatically reduced [4,5,6]. The inexpensive cytostatics such as hydrazine sulfate (HS), Sehydrin and 5-fluorouracil (5-FU), characterized by a low median lethal dose (LD50 )

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