Bielinska I. Hematological effects of antitumor and antianemic compounds maleimide derivative and heteropolynuclear complexes.

The hematologic response to the effect of the maleimide derivative and heteropolynuclear complexes with antitumor and antianemic activity was investigated. It was shown that the maleimide derivative acting under dimethylhydrazine-induced rat colon carcinogenesis prevents the development of anemia, which complicates the oncological diseases, and normalizes the monocytes and platelets blood amounts reducing the involvement of these cells into the tumor development progression. Hematotoxic effects of MI-1 after chronic use in effective antitumor dose don’t appear. Unlike 5-fluorouracil, which suppresses all germs of hematopoiesis, application of MI-1 in 5- and 10-fold doses causes the activation of erythropoiesis (reticulocytosis and erythroid hemopoietic cells amount increase), which can be a compensatory recipe for reducing the red blood cells viability. Activating effect of MI-1 on erythropoiesis is confirmed with joint action with cobalt chloride. MI-1 reduces the amount of leukocytes and monocytes in the blood, which is associated with their active output in the tissue, without oppression of leukopoiesis. MI-1 also suppresses thrombocytopoiesis. The suppression of neoplastic hematopoietic cells proliferative activity and induction of their apoptosis (monoblast human leukemic cells U-937, murine leukemic B cells L1210, human erythroleukemia cells K-562, idiopathic myelofibrosis blast cells) caused by MI-1 was firstly estimated. MI-1 stops cells in the proliferative rest phase Go/G1 and reduces the number of cells in the S-phase. The combination of MI-1 with the heteropolynuclear acetate complex of Cu/Cd with ethylenediamine [Cu(en)2[CdAc6] leads to 4-fold increase of antiproliferative effect when acting on K-562 cells. Interacting with membranes of erythrocytes, [Cu(en)2[CdAc6] reduces, the resistance of these cells to acid or alkali and suppresses K-562 cells proliferative activity. Interaction with red blood cells are the result of the action of the starting substance, not the products of its dissociation, which is confirmed by the various effects of the complex and its separate components on the erythrocytes stability. Heteropolynuclear Cu/Fe complex [Cu(dmen)2][Fe(CN)5(NO)] increases blood serum copper concentration and restores the iron one under its deficiency, as well as restores erythrocytic indices under experimental anemia, which indicates an anti-anemic property of the complex. The hematotoxic effect of the complex manifested by the hemolytic anemia development only when applied at dose of 100 mg/kg, which is 4-fold higher than the iron therapeutic dose and 200-fold higher than the copper one. The prospect of maleimide derivative MI-1 and heteropolynuclear complexeswith antitumor and antianemic activity, and low hematotoxicity was concluded.