Cardioprotective Effects of Subcutaneous Ebselen against Daunorubicin‐Induced Cardiomyopathy in Rats

• Published in: Basic & clinical pharmacology & toxicology Vol. 99; no. 6; pp. 412 - 417
• Main Authors: Saad, Sherif Y., Najjar, Tawfeeg A., Arafah, Maha M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.12.2006; Blackwell
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Antioxidants - pharmacology; Aspartate Aminotransferases - blood; Azoles - pharmacology; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathies - chemically induced; Cardiomyopathies - drug therapy; Cardiotonic Agents - pharmacology; Creatine Kinase, MB Form - blood; Daunorubicin - pharmacology; Glutathione - metabolism; Glutathione Peroxidase - blood; Glutathione Peroxidase - metabolism; Heart; Injections, Subcutaneous; L-Lactate Dehydrogenase - blood; Male; Medical sciences; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; Nitrates - metabolism; Nitrites - metabolism; Organoselenium Compounds - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Antineoplastic agent; Prostaglandin-endoperoxide synthase; Rat; Cardiomyopathy; Cardiovascular disease; Myocardial disease; Selenium Organic compounds; Daunorubicin; Heart disease; Subcutaneous administration; Enzyme; Subcutaneous; Rodentia; Cardioprotective agent; Enzyme inhibitor; Ebselen; Non steroidal antiinflammatory agent; Vertebrata; Antibiotic; Mammalia; Analgesic; Animal; Antipyretic; Anthracyclins; Oxidoreductases
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2006.pto_523.x

: Daunorubicin is an anthracycline antitumour agent that can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving daunorubicin‐induced superoxide anion production have been proposed. In the present study, we showed that ebselen a seleno‐organic compound exhibiting glutathione peroxidase‐like and antioxidant activities, significantly ameliorated daunorubicin‐induced cardiomyopathy. Subcutaneous administration of ebselen to daunorubicin‐treated rats showed significant improvement in serum cardiac indices including creatine kinase isoenzyme and lactate dehydrogenase as well as serum glutathione (GSH) peroxidase. Moreover, myocardium of daunorubicin/ebselen‐treated rats showed significant improvement in daunorubicin‐induced depletion of GSH peroxidase activity and reduced glutathione content, in addition to attenuation of daunorubicin‐induced increase in cardiac malondialdehyde production and total nitrate/nitrite concentration levels. These results were confirmed by histopathological examination of ventricles of daunorubicin/ebselen‐treated rats that revealed significant improvement of the characteristic cardiomyopathic changes induced by daunorubicin treatment. Interestingly, control rats treated with ebselen showed significant elevation in serum lactate dehydrogenase activity, cardiac malondialdehyde production and total nitrate/nitrite concentration levels compared with the untreated control animals. In conclusion, ebselen treatment significantly alleviates daunorubicin‐induced cardiomyopathy.