Modulating Effect of Carvedilol on Doxorubicin-Induced Cardiomyopathy and Hepatic Damage

Background: Doxorubicin is an anthracyclin antibiotic that is considered as one of the most effective antitumor agents. The clinical use of doxorubicin soon proved to be hampered by such serious problems as hepatotoxicity and most notably cardiomyopathy. Objectives: The current study aims at evaluating the efficiency of carvedilol as an adjuvant therapy with doxorubicin to protect against doxorubicin induced cardiomyopathy and hepatic damage. Materials and Methods: Animals were divided into normal group and doxorubicin -treated group injecting doxorubicin as a dose of 2.5 mg/kg/twice weekly/ 3 weeks. Doxorubicin treated animals were divided into two groups, one kept without further treatment (doxorubicin group) and second group, (doxorubicin + carvedilol), received carvedilol 1mg/kg/ 7 times over a period of 4 weeks including a dose before doxorubicin 1st dose. Creatine phosphokinase, lactate dehydrogenase, as cardiac damage markers, and alanine aminotransferase, as indicator of hepatic damage, were measured. Malondialdehyde and nitric oxide levels, as cardiac oxidative status indices, glutathione content, glutathione peroxidase, glutathione-S–transferase and superoxide dismutase activities, as measures for cardiac antioxidant capacity, were also investigated. Histopathological changes in cardiac and hepatic tissues of all groups were examined. Results and Conclusions: Our results revealed that doxorubicin caused oxidative stress which plays a major role in doxorubicin -induced cardiomyopathy and hepatic damage. Coadministration of carvedilol in concomitant with doxorubicin caused protection against doxorubicin–induced cardiomyopathy; however, it augmented doxorubicin -induced hepatic damage. Histopathological examination of cardiac and hepatic tissues supported the previous biochemical results. [Journal of American Science. 2010;6(12):20-32]. (ISSN: 1545-1003).