The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats

The iron chelating activity of deferoxamine (DFO) has been exploited to obt ain protection against the peroxidative damage in rat heart which was induc ed by the administration of an acute dose of doxorubicin (DXR, 25 mg kg(-1) , i.v.), The peroxidative lesions were evaluated both biochemically and his topathologically, 48 h after DXR administration. Abnormal biochemical chang es including a marked increase in the levels of serum creatine kinase isoen zyme (CK-MB), and lactate dehydrogenase (LDH), as well as elevated serum cr eatinine, blood urea nitrogen and transaminases (ALT and AST) levels were o bserved. Myocardial tissue from DXR treated rats showed a marked increase i n malondialdehyde (MDA) production and depletion of reduced glutathione (GS H) contents, Similar results were also observed in both kidney and liver ti ssues. Pretreatment of rats with DFO, given i.p. 30 min prior to DXR inject ion, substantially reduced the peroxidative damage in the myocardium, hepat ic and renal tissues and markedly lowered the serum CK-MB, LDH and the othe r biochemical variables. The protective effects obtained by DFO administrat ion, however, were not complete and did not reach those of the control grou p. The significant protection against DXR-induced cardiomyopathy by DFO was evident from the histopathological findings observed by light microscopy, DFO at a dosing level equivalent to 10-fold of that of DXR was useful to ob tain protective effects. Higher DFO dosing levels did not, however, show mo re improvement in the DXR-induced cardiotoxicity and at the same time exhib ited hepatoxicity which was confirmed by microscopical examination. These r esults strongly suggest that DFO protects against acute DXR-induced cardiot oxicity in a dose-dependent manner with recognizing the presence of mild DF O-related biochemical and cytological hepatic toxicity.