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