Biochemical and histopathological evaluations of the protective effects of the iron-chelator desferrioxamine against the cardiac and haematological toxicities of doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg/kg, i.v.) caused myocardial damage that manifested biochemically as an elevation of serum cardiac enzyme [glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase (LDH) and creatine phosphokinase (CPK)] and cardiac isoenzyme levels and histopathologically as a swelling and separation of cardiac muscle fibers. Doxorubicin caused severe leucopenia and decreases in red blood cell counts and haemoglobin concentrations at 72 h after its administration. Desferrioxamine treatment (250 mg/kg, i.p.) carried out 30 min before doxorubicin administration protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of levels of cardiac enzymes and isoenzymes and of red blood cell counts to normal values and by the absence of significant myocardial lesions. The findings of this study suggest that desferrioxamine can potentially be used clinically to prevent doxorubicin-induced cardiac and haematological toxicities.

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The calcium channel blocker verapamil increased the intracellular level of doxorubicin in Ehrlich ascites cells. The high cellular drug level was directly related to the enhancement of the cytotoxicity of the antitumor agent. Tumor-bearing mice pre-treated with verapamil showed a 2.3-fold increase in long-term survival effect of doxorubicin together with a pronounced inhibitory effect on tumor DNA, RNA and protein content. This study suggests the possible novel use of verapamil to enhance the antitumor activity of doxorubicin, allowing its dose, and consequently the serious side effects, to be reduced.

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