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 obtain protection against the peroxidative damage in rat heart which was induced by the administration of an acute dose of doxorubicin (DXR, 25 mg x kg(-1), i.v.). The peroxidative lesions were evaluated both biochemically and histopathologically, 48 h after DXR administration. Abnormal biochemical changes including a marked increase in the levels of serum creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH), as well as elevated serum creatinine, blood urea nitrogen and transaminases (ALT and AST) levels were observed. Myocardial tissue from DXR treated rats showed a marked increase in malondialdehyde (MDA) production and depletion of reduced glutathione (GSH) contents. Similar results were also observed in both kidney and liver tissues. Pretreatment of rats with DFO, given i.p. 30 min prior to DXR injection, substantially reduced the peroxidative damage in the myocardium, hepatic and renal tissues and markedly lowered the serum CK-MB, LDH and the other biochemical variables. The protective effects obtained by DFO administration, however, were not complete and did not reach those of the control group. 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 obtain protective effects. Higher DFO dosing levels did not, however, show more improvement in the DXR-induced cardiotoxicity and at the same time exhibited hepatoxicity which was confirmed by microscopical examination. These results strongly suggest that DFO protects against acute DXR-induced cardiotoxicity in a dose-dependent manner with recognizing the presence of mild DFO-related biochemical and cytological hepatic toxicity.
Saad
S Y
SY
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Najjar
T A
TA
Al-Rikabi
A C
AC
D000704:Analysis of Variance; D000818:Animals; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D002614:Chelating Agents; D004317:Doxorubicin; D003676:Deferoxamine