Amelioration of doxorubicin-induced cardiotoxicity by deferiprone in rats

• Published in: Canadian journal of physiology and pharmacology 2011-04, Vol.89 (4), p.269-276
• Main Authors: AMMAR, El-Sayed M, SAID, Shehta A, SUDDEK, Ghada M, EL-DAMARAWY, Sally L
• Format: Article
• Language: English
• Subjects: aconitine; Aconitine - pharmacology; Animals; Antibiotics; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - therapeutic use; Biological and medical sciences; cardiotoxicity; cardiotoxicité; Complications and side effects; Creatine Kinase, MB Form - metabolism; deferiprone; Dosage and administration; Doxorubicin; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; doxorubicine; Drug Interactions; défériprone; ECG; Electrocardiography; Electrocardiography - drug effects; Fundamental and applied biological sciences. Psychology; Glutathione - metabolism; Heart - drug effects; Heart diseases; Heart Diseases - chemically induced; Heart Diseases - metabolism; Heart Diseases - prevention & control; Heart Rate - drug effects; Iron - metabolism; Iron Chelating Agents - pharmacology; L-Lactate Dehydrogenase - metabolism; Male; Malondialdehyde - metabolism; Myocardium - metabolism; Prevention; Pyridones - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Risk factors; Rodents; Studies; Superoxide Dismutase - metabolism; Tachycardia, Ventricular - chemically induced; Toxicity; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y11-020

The therapeutic usefulness of doxorubicin (Dox), an anthracycline antibiotic used as an anticancer agent, is limited by its cardiotoxicity. Dox-induced cardiotoxicity is mainly attributed to accumulation of reactive oxygen species and interaction of Dox with cellular iron metabolism. The present study investigated the effects of the iron chelator deferiprone (Def) against Dox-induced cardiotoxicity in rats. Dox (15 mg/kg) was injected intraperitoneally as a single dose, and Def (10 mg/kg) was administered orally for 10 days. Dox showed cardiotoxicity as evidenced by increased heart rate, elevated ST segment, prolonged QTc interval, and increased T wave amplitude. In addition, Dox enhanced aconitine cardiotoxicity by decreasing its dose, producing ventricular tachycardia. Administration of Def significantly attenuated Dox-induced electrocardiographic changes. Cardiotoxicity of Dox was confirmed biochemically by a significant elevation in serum creatine kinase-MB and lactate dehydrogenase activities as well as by myocardial malondialdehyde and reduced glutathione contents. Moreover, Dox caused a significant decrease in myocardial superoxide dismutase activity. Administration of Def significantly attenuated the biochemical changes. These results suggest that Def might be a potential cardioprotective agent against Dox-induced cardiotoxicity.