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International Journal of Physiology and Pathophysiology
SJR: 0.116

ISSN Imprimir: 2155-014X
ISSN On-line: 2155-0158

Archives: Volume 1, 2010 to Volume 9, 2018

International Journal of Physiology and Pathophysiology

DOI: 10.1615/IntJPhysPathophys.v6.i3.30
pages 191-201

Hematological Effects of Protein Kinases Inhibitor Maleimide Derivative in Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats

Iryna V. Byelinska
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Oksana V. Lynchak
Kyiv Taras Shevchenko National University, Kyiv, Ukraine
Taras V. Rybalchenko
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
Oksana M. Gurnyak
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine


The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2, 5-dione) on the blood cells of rats with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied. It has been revealed that the introduction of MI-1 in a dose of 2.7 mg / kg for 20 weeks prevents anemia which accompanies cancer and complicates the course of the latter. This is evidenced by the reduction in the number of reticulocytes (0.19[0.15; 0.21]·1012/l) and restitution of the content (18.02 [17.44;19.03] pg) and concentration (309.42 [292.38;318.27] g/l) of hemoglobin in the erythrocytes to the control values (0.17 [0.15;0.19], 18.31 [17.95;18.45]), 310.78 [306.25;316.18], respectively) in contrast to the group injected with DMH (0.28 [0.24;0.39]; 17.50 [17.00;17.96]; 288.10 [284.71;303.73], respectively). MI-1 normalizes the count of monocytes (1.40 [0.95; 2.50] ·109 /l) and platelets (646.32 [575.23; 700.50] ·109 /l) in the blood after 26 weeks of experiment. In subjected to DMH rats, these parameters are significantly higher (1.97 [1.52; 2.58], 783.90 [687.64; 922.27], respectively) compared to the 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 tumor progression and metastasis. Reduced monocytosis and thrombocytosis may be mediated by: 1) a decrease in the number of tumors and the area of colon lesions and, consequently, the influence of their cytokines on hematopoietic tissue; 2) an inhibition of proliferation and differentiation of hematopoietic progenitor cells through inhibiting receptor protein kinases of vascular endothelial and epidermal growth factors and non-receptor PDK1-, Src- and Syk-protein kinases that are involved in hematopoiesis and carcinogenesis.