Modulatory effect of dopamine on doxorubicin-induced myelosuppression

Bone marrow suppression is a dose-limiting toxicity of anticancer drugs. We have investigated in this study whether dopamine (DA), a catecholamine neu rotransmitter, 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 S wiss mice. The animals received a single intravenous injection of DXN (25 m g/kg) 24h after last injection of DA. DXN caused an immediate and sharp fal l in total leucocyte, neutrophil, lymphocyte and platelet counts in periphe ral 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 o f megakaryocytes (MK) and their precursors (SAChE+cells), and stimulation o f pulmonary MK. Thrombopoiesis, assessed in terms of incorporation of S-35 by platelets, was stimulated in DA-treated mice. Moreover. DA pretreatment partially protected the day 12 colony-forming unit spleen (CFU-S-12) from t he lethal effects of DXN, and substantially reduced the mortality of the tr eated animals. The results demonstrate protection by DA against the myelosu ppressive effect of DXN.