THE HEMATOLOGICAL EFFECTS OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE AND 5‑FLUOROURACIL
I.V. Byelinska, T.V. Rybalchenko, S.M. Tsyvinska, V.K. Rybalchenko
Taras Shevchenko National University of Kyiv, Ukraine
The effect of the protein kinase inhibitor maleimide derivative
with antitumor activity (inhibits colorectal
carcinogenesis) at five fold (13.5 mg/kg, ~ 5.10‑4 mol/l in the
blood) and ten fold (27 mg/kg, ~ 10.10-4 mol/l in the blood) the
effective dose for 14 days on blood cells of rats in comparison with cytostatic 5‑fluorouracil (5‑FU) have been studied. It is
shown that MI‑1 causes activation of erythropoiesis, as evidenced
by an increase in reticulocyte count and hematocrit and
hemoglobin concentration in the blood without changing of
morphofunctional state of erythrocytes: volume, content and
concentration of hemoglobin. Comparison drug 5‑FU at the
concentration ~ 10×10‑4 M in the blood (which correspod the
effective dose 8.6 mg/kg) inhibits erythropoiesis, as evidenced
by a decrease in the erythrocyte and reticulocytes count in
the blood. MI-1 at 5 and 10 times the effective dose cause a
trend to reduce the number of leukocytes and monocytes, and
platelets in the blood. Count of basophilic, eosinophilic and
neutrophilic granulocytes and lymphocytes in the blood do
not change. 5‑FU at the appropriate concentration reduces the
number of leukocytes, lymphocytes, monocytes, neutrophils
and platelets in the blood. Five fold (45 mg/kg) the effective
dose of 5-FU causes 100% mortality of rats after the first week
of administration. In the blood of animals 5 days after the influence
of 5-FU reduces the number of erythrocytes, leukocytes,
lymphocytes, monocytes and platelets and tend to reduce of
neutrophils number. Thus, a maleimide derivative MI-1 with
antitumor activity has low, as compared to high toxic 5‑FU,
haematotoxicity at the 10 fold the effective dose, that is an
advantage in its use and promising for further studies
maleimide derivative; protein kinases inhibitor; 5-fluorouracil; erythrocytes; leukocytes; platelets
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