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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. 2014; 60(4): 40-49


Hematological effects of the protein kinase inhibitor maleimide derivative in dimethylhydrazin E-induced colorectal carcinogenesis of rats

Bielins'ka IV, Lynchak OV, Rybal'chenko TV, Hurniak OM

    Taras Shevchenko National University, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz60.04.040

Abstract

The effect of the protein kinase inhibitor maleimide derivative (MI- 1, 1.(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole- 2,5-dione) on blood cells of rats with 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis has been studied. Administration of MI-1 at 2.7 mg/kg for 20 weeks on DMH-induced carcinogenesis prevents anemia, which is a consequence of cancer and complicates it. This is confirmed by a reduction in the number of reticulocytes (0,19 (0,15;0,21)Ѓ~1012/l) and restoration of mean corpuscular hemoglobin (18,02 (17,44;19,03) pg) and mean corpuscular hemoglobin concentration (309,42 (292,38;318,27) g/L) to a control value (0,17 (0,15;0,19), 18,31 (17,95;18,45), 310,78 (306,25;316,18), respectively) in contrast to the group DMH (0,28 (0,24;0,39); 17,50 (17,00;17,96); 288,10 (284,71;303,73), respectively). MI-1 normalizes the number of monocytes (1,40 (0,95;2,50)Ѓ~109/L) and platelets (646,32 (575,23;700,50)Ѓ~109/L) in the blood after 26 weeks of experiment; in the DMH group, the values are significantly higher (1,97 (1,52;2,58), 783,90 (687,64;922,27), respectively) as compared to control group (1,23 (0,94;1,68), 629,34 (590,19;711,48), respectively). MI-1 reduces the involvement of these cells in the tumors progression and metastasis. Reduction of the monocytosis and thrombocytosis may be mediated by: 1) a decrease in the number and size of tumors and, consequently, the influence of their cytokines on hematopoietic tissue; 2) suppression of proliferation and differentiation of hematopoietic progenitor cells through inhibiting of receptor protein kinases of vascular endothelial and epidermal growth factors and nonreceptor PDK1-, Src- and Syk- kinases, that are involved in hematopoiesis and carcinogenesis.

Keywords: maleimide derivative, protein kinases inhibitor,1,2-dimethylhydrazine-induced colon carcinogenesis,erythrocytes, leukocytes, platelets

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