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

Abstract

The effect of the protein kinase inhibitor maleimide derivative (MI-, 1, 1-(4-Cl-benzyl)-3-CI-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-I1 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 numberofreticulocytes (0,19(0,15;0,21)x 10(12)/1)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-I normalizes the number of monocytes (1,40 (0,95;2,50)x 10(9)/L) and platelets (646,32 (575,23;700,50)xl10(9)/L) in the blood after 26 weeks ofexperiment; 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 non-receptor PDKI-, Src- and Syk- kinases, that are involved in hematopoiesis and carcinogenesis.