The Cardio protective Role of Carvedilol and Selenium against Doxorubicin­ Induced Cardio toxicity in Rats

Abstract

The present study was performed to investigate the effect of doxorubicin chronic administration on certain biochemical paramters in heart of rats. It was, also, extended to explore the role of pre-administration of antioxidants such as carvedilol and selenium in ameliorating doxorubicin cardiomyopathy. In this study, these protective agents were administered either separately or in combination using half dose of carvedilol. Male Wistar albino rats were divided into normal control which received only normal saline and doxorubicin induced cardiotoxocity groups. Doxorubicin was administered i.p. in six equal doses each of 2.5 mg/kg b.w over a period of three weeks in a cumulative dose of 15mglkg body weight .Doxorubicin treated animals were further divided into four groups. The first was kept without further treatment termed Dox-group. The second group is (Dox + Car) which received carvedilol i.p. in a dose of lmg/kg body weight 7 times over a period of four weeks including a dose before doxorubicin first dose. The third group (Dox + Se) received 0.5 mg/ kg body weight of Na selenite orally three times a week for twenty eight days including one week before doxorubicin first dose. The fourth group (Dox +112 Car + Se) received a combination of cavedilol in its half dose 0.5 mglkg body weight in addition to selenium full dose. Results of the present study revealed that repeated administration of doxorubicin resulted in cardiotoxicity manifested by ultrastructural alternations and significant elevation of serum LDH and CK. Doxorubicin administration resulted in increased oxidative and nitrosative stress indicated by increased cardiac MDA and NO levels , decreased GSH content in heart and disturbed activities of cardiac antioxidant enzymes SOD, GPx and GST. Supplementation of doxorubicin treated rats with selenium offered partial normalization in altered parameters .Meanwhile carvedilol coadministration either alone using its full dose or in combination with selenium using carvedilol half dose effectively relieved doxorubicin induced histopathological alternations and biochemical disturbances .In •addition to protective role against doxorubicin cardiomyopathy,The combination of selenium and a low dose of carvedilol has an extra advantage of reducing carvedilol side effects especially hepatotoxicity.