Effect of maleimide derivative inhibitor of protein kinases with antitumor activity on megakaryocytopoiesis in rats

L. Byelinska

Abstract


The effect of the inhibitor protein kinases maleimidederivative MI-1 (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione) with antitumor activity at doses at five times (13.5 mg/kg) and ten times (27 mg/kg) the effective dose for subacute exposure onmorphofunctional state of bone marrow megakaryocytes and platelet count in the blood of rats have been studied. MI-1 at the dose of 2.7 mg/kg (effective antitumor – decreases the number of colon tumors and the affected area of the colon of rats) during 14 days does not changethe count of plateletsin the blood and megakaryocytes, which form platelets, in the bone marrow comparedto the untreated control group. Increasing the dose of MI-1 to 5- and 10-times (13.5 and 27 mg / kg, respectively) leads to a decrease in the number of platelets in the blood (p=0.012; p=0.027, respectively) without changes in the number of megakaryocytes in the bone marrow compared to the untreated control. Analysis of the morphofunctional state of megakaryocytes at the10-fold increased dose of MI-1 indicatesan increase in immature promegakaryocytes, hyposegmented and micromegakaryocytes to reduce background mature polichromatophilicand oxyphilicmegakaryocytes and hypersegmented and giant cells. Megakaryocytopoiesis revealed changes under the influence of MI-1 in 10-times the effective dose testify delay differentiation of megakaryocytes, which causes a decrease platelet production and, including their concentration in the altered areas of microcirculation in various tissues, leading to thrombocytopenia in the blood of rats.

Keywords


maleimide derivative; protein kinases inhibitor; megakaryocytes; platelets

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DOI: http://dx.doi.org/10.17721/2616_6410.2017.22.16-20

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