Morphine is protective against doxorubicin-induced cardiotoxicity in rat

Abstract

Doxorubicin (DOX) is an anthracycline antibiotic that is widely used as a chemotherapeutic agent. However, usefulness of this agent is limited due to its cardiotoxic effects. The aim of this study was to investigate the potential protective effects of morphine against DOX-induced cardiotoxicity in rats. Male Sprague-Dawley rats were treated with morphine (10mg/kg i.p.) and/or DOX (1.25mg/kg i.p.), 4 times per week, for 4 weeks. Mortality, general condition and body weight of the animals were observed during the whole treatment, and for a further 4-week period, until the end of experiment. Evaluation of cardioprotective efficacy of morphine was performed by analyzing the electrocardiographic parameters and contractility force of left ventricular papillary muscle. Necropsy was also performed at the end of the experiment, and heart excision, weight and macroscopic examination were done before histological evaluation. Doxorubicin caused heart disturbances manifested by prominent electrocardiographic changes (S(alpha)-T prolongation), decrease of the heart contractility, as well as histopathologically verified myocardial lesions. The changes in heart parameters were accompanied by 50% mortality rate, significant decline in body mass and severe effusion intensity score of the animals. Application of morphine before each dose of DOX either significantly reduced or completely prevented its toxic effects. Therefore, since morphine had very good protective effects against a high dose of DOX given as a multiple, low, unitary dose regimen, not only on the heart but on the whole rat as well, it could be recommended for further investigation in this potentially new indication for clinical application.