Effect of daunorubicin drug with and without cimetidine on the nucleated cells of bone marrow of balb/c mouse

Abstract

Introduction: Hematopoiesis is an on going process mammalian marrow system. A few cells from the nucleated cells of bone marrow are hematopoietic cells which include primary stem cells, precursor cells and progenitor cells. Primary stem cells and progenitor cells are able to produce colonies in culture medium (CFU-C) and irradiated mouse spleen (CFU-S). A hematopoietic cell is alive and active when it can produce colonies and proliferate otherwise it is practically a dead cell. These cells are subject to damage from chemical or physical agents such as chemothrapeutic drugs or ionizing radiation . Materials and Methods: In the present research 150 balb/c mice were bought from Razi institute, as well as daunorubicin, which is an important drug for treatment of acute myeloid leukemia, was used as a destructive agent for bone marrow and cimetidine was used as a protective agent for bone marrow against daunorubicin. In this research one of the methods of in vivo stem cell assay. Which is called spleen colony assay, is used. The basis of this method is injection of bone marrow hematopietic cells into irradiated mouse (Supralethal irradiation ). 8 to 10 days after injecting bone marrow cells stem cells produce colonies in spleen of irradiated mouse each colony represents one primary hematopoietic cell. Findings: By the method of spleen colony assay it was shown that daunorubicin at doses of 5 to 20 mg/kg will decrease the number of colonies formed in spleen . On the other hand it was shown that cimetidine in concentration of 15 mg/kg will decrease the toxic effects of these drugs and will cause an increase in spleen colonies and relative survival of mouse bone marrow cells. Cimetidine will possibly cause its relieving effects by neutralizing histamine free radicals through decreasing the activity of cytochrome P450 and increasing glutathione and increasing glutathione activity. Conclusion: Cimetidine is able to reduce the cytolytic and cytotoxic effect of daunorubicin on nucleated cells of mouse bone marrow.