Résumé
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 ?-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 ?-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 ?-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 ?-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.
Résumé
Background: The dosage of highly efficacious anti-cancer drug doxorubicin (DOX) is often constrained as limited data exists on its hepatotoxic potential. The present study not only evaluated the extent of its hepatotoxicity but also aimed at curtailing it, by administration of two drugs i.e. trimetazidine and lovastatin, both of which are otherwise known for their cardioprotective benefits.Methods: The study was a lab-based randomized controlled study on mice. Acute toxicity was introduced with DOX injected intraperitoneally at a dose of 10 mg/kg and it was protected by oral administration of trimetazidine and lovastatin, both in a dose of 10 mg/kg. The protective drugs were both given for five and ten consecutive days in short and long term study designs whereby DOX was administered on the third and eighth days of the respective studies.Results: Doxorubicin administration caused significant hepatotoxicity reflected by markedly raised biomarkers (serum alanine aminotransferase and aspartate aminotransferase) and mild inflammation of liver parenchyma with a score of 4 as per Ishak grading scale. The changes were significantly attenuated by both the protective drugs in the ten days study design. However, in the five days study, lovastatin exhibited more significant hepatoprotection than trimetazidine.Conclusions: Pretreatment with two commonly available, cost effective and safe drugs can effectively prevent a potentially life-threatening adverse effect of DOX. This approach might prove very convenient for the health care providers as well as for the patients without burdening the economics.