Published 4 issues per year
ISSN Print: 2155-014X
ISSN Online: 2155-0158
Hematological Effects of Protein Kinases Inhibitor Maleimide Derivative in Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats
ABSTRACT
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.