Comparison of protective effects of carvedilol and α-tocopherol on doxorubicin-induced cardiotoxocity

摘要

Background: Doxorubicin, an effective anticancer drug used to treat multiple solid tumours and childhood malignancies since many decades but its cardiac adverse effects limits its use in full therapeutic dose. The mechanism involved in cardiotoxicity is apoptosis of cardiomyocytes due to reactive oxidative stress. The study was conducted to compare the cardioprotective effects of carvedilol and α-Tocopherol and to detect myocardial injury at early stage. Methods: Cardiotoxicity was produced in a group of rabbits by single intravenous injection of doxorubicin; control group was treated with normal saline only. Third and fourth groups were pretreated with carvedilol 30 mg/kg bodyweight and α-Tocopherol 200 mg/kg bodyweight respectively for ten days before injection of doxorubicin. Results: Doxorubicin produced marked cardiotoxicity represented by raised levels of serum biomarkers (cTnI, LDH and CK-MB) and severe necrosis of cardiomyocytes on microscopic examination. Carvedilol and α-tocopherol pretreatment resulted in decreased serum levels of biomarkers and improved the histological picture of heart tissue. Conclusions: The outcome of doxorubicin chemotherapy can be made successful with the concurrent use of carvedilol or α-tocopherol. Although carvedilol has more pronounced cardioprotective effects perhaps due to its antioxidant activity in addition to antiapoptotic, antiproliferative and anti-inflammatory effects. Furthermore the quantitative cTnI estimation for detection of cardiotoxicity at early stage can lead to significant economic impact in management of cancer.