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Home Archive 2016 № 3 CALIX[4]ARENE C-145 EFFECTS ON СELLULAR HAEMOSTASIS V. O. Chernyshenko, D. S. Korolova, T. V. Nikolaienko, V. Е. Dosenko, D. O. Pashevin, V. I. Kalchenko, S. O. Cherenok, N. N. Khranovska, L. V. Garmanchuk, E. V. Lugovskoy, S. V. Komisarenko
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ISSN 2410-7751 (Print)
ISSN 2410-776X (on-line)

"Biotechnologia Acta" V. 9, No 3, 2016
https://doi.org/10.15407/biotech9.03.037
Р. 37-43, Bibliography 23, English
Universal Decimal Classification: 577.112:612.115

CALIX[4]ARENE C-145 EFFECTS ON СELLULAR HAEMOSTASIS

V. O. Chernyshenko1, D. S. Korolova 2, T. V. Nikolaienko2, V. Е. Dosenko 3, D. O. Pashevin 3, V. I. Kalchenko 4, S. O. Cherenok 4, N. N. Khranovska 5, L. V. Garmanchuk2, E. V. Lugovskoy 1, S. V. Komisarenko 1

1 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv
2ESC «Institute of Biology» Taras Shevchenko National University, Kyiv
3 Bohomolets Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
4 Institute of Bioorganic Chemistry and Petrochemistry    of the National Academy of Sciences of Ukraine, Kyiv
5 National Cancer Institute   of Ministry of Health of Ukraine, Kyiv

The aim of the research was to study a potential antithrombotic sodium salt of calix[4]arene-methylene-bis-phosphonic acid (С-145) — on activation and aggregation of platelets in vivo, as well as on proliferation and apoptosis of endothelial cells in the cell culture.

Effects of calix[4]arene С-145 estimated in vitro after addition to the platelet rich plasma, and in vivo after intravenous injection into rabbit bloodstream in equivalent amounts (46 μM). Aggregation of platelets was induced by adenosine diphosphate and detected using aggregometer Solar AP2110. Platelet shape and cytoplasmic granularity were monitored on COULTER EPICS XL Flow Cytometer. The level of tissuetype plasminogen activator — tPA — was estimated using enzyme-linked immunosorbent assay ELISA. Effects of calix[4]arene C-145 on culture of endotelial cells cells was studied using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide — MTT-test. The population of proliferative pool of cells (G2/M+S) was determined using flow cytometry.

Aggregometry and flow cytometry showed that calix[4]arene C-145 did not activate platelets nor affect their aggregation in vitro. However intravenous injection of calix[4]arene C-145 into the bloodstream of healthy rabbits leads to strong inhibition of platelet aggregation and changes of shape and granularity of most of the platelets after 2 hours of administration. Any additional appearance of endothelial cells activation marker tPA in vivo and any inhibition of calix[4]arene C-145 on proliferation of endothelial cells in cell culture did not observe.

So calix[4]arene C-145 had strong anti-platelet effect in vivo that was not a result of their direct action on platelets or endothelial cells in vitro. This allowed to assume the possibility of calix[4]arene C-145 use as an effective antithrombotic agent.

Key words: calix[4]arene, haemostasis, antithrombotic drugs, fibrin polymerization.

© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2016

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Home Archive 2016 № 3 CALIX[4]ARENE C-145 EFFECTS ON СELLULAR HAEMOSTASIS V. O. Chernyshenko, D. S. Korolova, T. V. Nikolaienko, V. Е. Dosenko, D. O. Pashevin, V. I. Kalchenko, S. O. Cherenok, N. N. Khranovska, L. V. Garmanchuk, E. V. Lugovskoy, S. V. Komisarenko

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