Change in the number of CD117+ stem cells, cytogenetic and cytokinetic parameters under the use of candesartan, candesartan cilexetil and resveratrol in vitro

A. Beliayeva, L. Garmanchuk
Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv


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.


Candesartan cilexetil, candesartan, resveratrol, CD117+ stem cells, apoptotic cells, micronuclei and cell cycle parameters.

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Zhao D., Liu H., Dong P. A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension. Clin Exp Hypertens 2019;41(1):75-79.

De Rosa M., Chiariello M. Candesartan improves maximal exercise capacity in hypertensives results of a randomized placebo-controlled crossover trial. J. Clin Hypertens. 2009; 11 (4): 192–200.

Naeshiro I., Sato K., Chatani F., Sato S. Possible mechanism for the anemia induced by candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, in rats. Europ J of Pharmacology. 1998; 354 (2/3): 179–187.

Adi Y., Rachel A., Maia Y., Marina K. Holz. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol. 2017; 1: 35.

Brisdelli F., D'Andrea G., Bozzi A.Resveratrol: a natural polyphenol with multiple chemopreventive properties // Curr Drug Metab. 2009 Jul;10(6):530-46.

Riba A., Deres L., Sumegi B., Toth K., Szabados E., Halmosi R. Cardioprotective effect of resveratrol in a postinfarction heart failure model. Oxid. Med. Cell. Longev. 2017;2017:6819281. doi: 10.1155/2017/6819281

Zhigang Z., Li Gao., Yanyan C., Jing Jiang., Yan Chen., Huijie Jiang., Hongxiang Yu., Anshan Shan., Baojing Cheng. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure. BioMed Research International. Volume 2014, Article ID 617202, 7 pages.

Yan F., Sun X., Xu C. Protective effects of resveratrol improve cardiovascular function in rats with diabetes. Exp. Ther. Med. 2018;15:1728–1734. doi: 10.3892/etm.2017.5537.

Orlic D., Kajstura J., Chimenti S., Jakoniuk I., Anderson S., Li B., Pickel J., McKay R., Nadal-Ginard B., Bodine D., Leri A., Anversa P. Bone marrow cells regenerate infracted myocardium. Nature. 2001; 410 (6829): 701–705.

Orlic D., Hill J., Arai A. Stem cells for myocardial regeneration. Circulation Research. 2002; 91: 1092–1102.

Orlic D., Kajstura J., Chimenti S., Limana F., Jakoniuk I., Quaini F., Nadal-Ginard B., Bodine D., Leri A., Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. of the Nat. Acad. of Sciences of the USA. 2001; 98 (18): 10344–10349.

Chenxia Hu., Lanjuan Li. The application of resveratrol to mesenchymal stromal cell-based regenerative medicine Stem Cell Research Therapy 2019 volume 10,Article number: 307

Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D., Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8(4):315–7.

Salem H., Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells (Dayton, Ohio). 2010;28(3):585–96.

Wang F., Hu Z., Liu X., Feng J., Augsburger R., Gutmann J., Glickman G. Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells.

Arch Oral Biol. 2019;97:116–121.

Received: 04.10.2019

Revised: 04.11.2019

Signed for the press: 04.11.2019



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