Abstract

Due to the increase in cardiovascular disease, it is urgent to research new effective and safe drugs and their combinations. Candesartan cilexetil, an angiotensin II receptor antagonist, is a precursor to the active form of candesartan. However, these antiischemic drugs have a cytotoxic effect, affecting the antioxidant system. Therefore, to prevent the cytotoxic effect is the need to use antioxidants. To study the effect of candesartan cilexetil, candesartan and resveratrol antioxidant in various doses and combinations on CD117+ stem cell mobilization, on the number of apoptotic and micronucleated cells and cell cycle parameters in vitro. Bone marrow cells isolated from C57Bl / 6 mice were selected for experiments. After incubation for 2 days with the means in different concentrations and combinations, the biological characteristics of the stem cells were determined. Flow cytometry was used to analyze the number of CD117 + stem cells, the ratio of apoptotic cells, cells with micronuclei and cell cycle parameters when using candesartan cilexetil, candesartan, and resveratrol in vitro. It was found that using candesartan cilexetil with resveratrol and candesartan with resveratrol promotes the formation of CD117 + stem cells from 1.2 times to almost 2 times compared with controls and 1.5 and 2.5 compared with cytostatics. Candesartan cilexetil and candesartan were cytotoxic, while resveratrol reduced the adverse effects of the substances in combination. Combination of candesartan cilexetil with resveratrol; Candesartan with resveratrol significantly increased CD117+ stem cell count and was not cytotoxic.

Highlights

  • The incidence of cardiovascular diseases has increased several times in many countries all over the world

  • We investigated the effect of candesartan cilexetil, candesartan and resveratrol on changes in the number of CD117+ stem cells

  • It was shown that candesartan cilexetil at 1.5 μg/ml dose didn't stimulate generation of CD117+ stem cells in vitro as compared to the control

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Summary

Introduction

The incidence of cardiovascular diseases has increased several times in many countries all over the world. It's necessary to study new methods of treatment of cardiovascular diseases, investigate new effective and safe drugs and combinations thereof. Candesartan cilexetil is an angiotensin II receptor antagonist. It is a pro-drug, which converted to the active form candesartan during absorption from the gastrointestinal tract. It is used as a long-term antihypertensive agent [1]. Resveratrol, a naturally occurring polyphenol, shows pleiotropic health beneficial effects, including antioxidant, anti-inflammatory, anti-aging, cardioprotective and neuroprotective activities [4,5,6]. It's found that this substance decreases the synthesis of lipids in liver and eico-

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