Animal study of Anthracycline-induced cardiotoxicity and nephrotoxicity and evaluation of protective agents

Abstract

Study background: Anticancer chemotherapy Anthracycline (ANT) antibiotics associated with cardiac and renal toxicity which represents serious complication. In this study, the protective effect of the 2 beta-blockers carvedilol and nebivolol were tested in a rat model of ANT induced cardio and renal-toxicity by repeated intraperitoneal doxorubicin (Dox) administration. Methods: Six groups of animals were used, each 8 rats divided as control group-received intraperitoneal saline every other day; control carvedilol: rats received carvedilol dose 30mg/kg/day orally; control nebivolol: rats received nebivolol 1mg/kg/day orally; doxorubicin alone: a dose of 3 mg/kg/day was administered intraperitoneal every other day; doxorubicin + carvedilol: carvedilol started at the same day with Dox; doxorubicin + nebivolol: nebivolol started at the same day with Dox. All substances were administered for 12 days. Detection & quantification of doxorubicin-induced heart and renal damage and therapeutic action of beta-blockers was done using Langendorff's technique, echo-cardiographic function examinations, serum creatinine, total proteins and histopathology. Results: The administration of doxorubicin in the dose of 3 mg/kg/day for 12 days produced pronounced heart impairment, as well as renal nephrotoxic changes. Significant reduction of Doxo-cardiotoxicity and nephrotoxicity in Nebivolol-treated animals more than Carvedilol treated animals. Conclusions: Coadministration of either carvedilol or nebivolol with doxorubicin was able to ameliorate up to almost contradict doxorubicin-induced myocardial injury, glomerular filtration disturbance and renal tubular damage with upper hand for nebivolol. So, they can be considered a feasible candidate to protect against nephrotoxicity & cardiotoxicity commonly encountered with doxorubicin treatment. © 2011 Shafik AN, et al.