Modulatory Effect of Dopamine on Doxorubicin-induced Myelosuppression

Abstract

Bone marrow suppression is a dose-limiting toxicity of anticancer drugs. We have investigated in this study whether dopamine (DA), a catecholamine neurotransmitter, could alleviate the haematotoxicity of doxorubicin (DXN), an established anticancer drug having profound myelotoxicity. DA was injected intraperitoneally at a dose of 50 mg/kg/day for five consecutive days in Swiss mice. The animals received a single intravenous injection of DXN (25 mg/kg) 24h after last injection of DA. DXN caused an immediate and sharp fall in total leucocyte, neutrophil, lymphocyte and platelet counts in peripheral blood, and nucleated cells in femur and spleen. DA treatment before DXN substantially reduced the degree and duration of these abnormalities, and also mediated a significant rise in the number of cells of granulocyte and erythroid lineage in the spleen. DA-pretreated mice showed early recovery of megakaryocytes (MK) and their precursors (SAChE+ cells), and stimulation of pulmonary MK. Thrombopoiesis, assessed in terms of incorporation of 35S by platelets, was stimulated in DA-treated mice. Moreover, DA pretreatment partially protected the day 12 colony-forming unit spleen (CFU-S12) from the lethal effects of DXN, and substantially reduced the mortality of the treated animals. The results demonstrate protection by DA against the myelosuppressive effect of DXN.