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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(4): 37-47

THE HEMATOLOGICAL EFFECTS OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE AND 5‑FLUOROURACIL

I.V. Byelinska, T.V. Rybalchenko, S.M. Tsyvinska, V.K. Rybalchenko

    Taras Shevchenko National University of Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz63.04.037


Abstract

The effect of the protein kinase inhibitor maleimide derivative (MI‑1, 1‑(4‑Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1Hpyrrole-2,5-dione) with antitumor activity (inhibits colorectal carcinogenesis) at five fold (13.5 mg/kg, ~ 5.10‑4 mol/l in the blood) and ten fold (27 mg/kg, ~ 10.10-4 mol/l in the blood) the effective dose for 14 days on blood cells of rats in comparison with cytostatic 5‑fluorouracil (5‑FU) have been studied. It is shown that MI‑1 causes activation of erythropoiesis, as evidenced by an increase in reticulocyte count and hematocrit and hemoglobin concentration in the blood without changing of morphofunctional state of erythrocytes: volume, content and concentration of hemoglobin. Comparison drug 5‑FU at the concentration ~ 10×10‑4 M in the blood (which correspod the effective dose 8.6 mg/kg) inhibits erythropoiesis, as evidenced by a decrease in the erythrocyte and reticulocytes count in the blood. MI-1 at 5 and 10 times the effective dose cause a trend to reduce the number of leukocytes and monocytes, and platelets in the blood. Count of basophilic, eosinophilic and neutrophilic granulocytes and lymphocytes in the blood do not change. 5‑FU at the appropriate concentration reduces the number of leukocytes, lymphocytes, monocytes, neutrophils and platelets in the blood. Five fold (45 mg/kg) the effective dose of 5-FU causes 100% mortality of rats after the first week of administration. In the blood of animals 5 days after the influence of 5-FU reduces the number of erythrocytes, leukocytes, lymphocytes, monocytes and platelets and tend to reduce of neutrophils number. Thus, a maleimide derivative MI-1 with antitumor activity has low, as compared to high toxic 5‑FU, haematotoxicity at the 10 fold the effective dose, that is an advantage in its use and promising for further studies

Keywords: maleimide derivative; protein kinases inhibitor; 5-fluorouracil; erythrocytes; leukocytes; platelets

Full text: (PDF, in Ukrainian)

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