Cardioprotective effects of Rhododendron arboreum leaf extract against Doxorubicin-induced cardiotoxicity in Wistar rats by modulating electrocardiographic and cardiac biomarkers

Abstract

BackgroundCardiotoxicity and related complications are well-known adverse effects of anticancer drugs like doxorubicin (DOX). A medicinal plant called Rhododendron arboreum is used by traditional healers of Sikkim in the treatment of heart ailments and has also been reported for widespread therapeutic effects in many clinical studies. Thus the present study has been designed to evaluate the protective effects of Rhododendron arboreum leaf extract (RALE) against DOX-induced cardiotoxicities.MethodsCommencement of research with the collection of the Rhododendron arboreum leaves and drying it in the shade, the extraction was performed using the Soxhlet method with an ethanolic solvent. The phytoconstituents of the RALE were then quantified and qualitatively evaluated. Doxorubicin-induced cardiotoxicity was carried out using four groups consisting of six animals each. Doxorubicin was administered with a dose of 3 mg/kg injected intraperitoneally (i.p.) on the 1st,7th,14th,21st and 28th day of cumulative dose of 15 mg/kg throughout the experimental period with RALE treatment (250 mg/kg and 100 mg/kg) orally for 28 days. The influence of the treatment was analyzed by quantification of cardiac biomarkers and electrocardiographic method.ResultsThe serum levels of cardiac biomarkers such as Lactate Dehydrogenase (LDH), Creatine kinase-N-acetyltransferase (CK-NAC), Creatine kinase-MB (CK-MB), Aspartate Transaminase (AST), Alanine Transaminase (ALT), which were elevated due to DOX-induced cardiotoxicity were significantly reduced in all RALE (250 mg/kg and 100 mg/kg) treated groups. Similarly, the electrocardiographic changes like prolonged QT interval, widening of QRS complex amplitude, undefined ST segment, arrhythmias and increased heart rate were also restored close to normal in all treated groups compared to the DOX control group.ConclusionFollowing the data observed during the study, results reported that R. arboreum possesses the free radical scavenging property, improved cardiotoxic laboratory parameters and restored reversible cellular injury due to existing of the principle constituent’s impact on proinflammatory mediators.