EARLY DETECTION OF DOXORUBICIN-INDUCED CARDIOTOXOCITY AND ITS PREVENTION BY α-TOCOPHEROL

Doxorubicin-Induced Cardiotoxocity Detection

Abstract

Objective: To detect doxorubicin-induced myocardial injury by quantitative estimation of cardiospecific protein, Cardiac Troponin I (cTnI) at early stage and to evaluate the cardioprotective effects of α-Tocopherol.
Study Design: Lab based randomized controlled in-vivo study in rabbits.
Place and Duration of Study: Department of Pharmacology in collaboration with Pathology department, Army Medical College Rawalpindi, Pakistan from Jan 2012 to Dec 2012.
Material and Methods: Eighteen healthy male adult rabbits were used. Cardiotoxicity was induced by single intravenous injection of 12 mg/kg of doxorubicin in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pretreated with α- Tocopherol 200 mg/kg of body weight for ten days before injection of doxorubicin 12 mg/kg.
Results: Doxorubicin produced severe cardiotoxicity confirmed by markedly raised serum levels of cTnI, CKMB, LDH and grade 3 necrosis of the heart tissue in rabbits. The pre-treatment with α-Tocopherol resulted in improved serum levels of cTnI and the histological picture of heart tissue.
Conclusions: The quantitative cTnI estimation for detection of cardiotoxicity at subclinical level can lead to significant economic impact in management of cancer patients because the troponin-negative subjects can be excluded from long term cardiac monitoring programs, which require high cost imaging techniques. Furthermore, the outcome of most potent and widely used doxorubicin chemotherapy can be made successful with the concurrent use of α-Tocopherol.