Rutin attenuates doxorubicin-induced cardiotoxicity via regulating autophagy and apoptosis

Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activitywhichmay regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discov- ered. In this study,we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potentialmechanisms of protective effects of rutin against cardiomyocyte death.Weanalyzed cardiac tissues at the time point of 8 weeks after doxorubicin treatment. The results by echocardiography, TUNEL staining, Masson's trichrome staining aswell asWestern blot analysis revealed that doxorubicin induced remarkable car- diacdysfunctionand cardiotoxicity inmice hearts and cardiomyocytes,whichwere alleviated by rutin treatment. Western blot analysis indicated that the underlying mechanisms included inhibition excessive autophagy and apoptosismediated by Akt activation. Collectively, our findings suggest that suppression of autophagy and apo- ptosis by administration of rutin could attenuate doxorubicin-induced cardiotoxicity, which enhances our knowledge to explore newdrugs and strategies for combating this devastating side effect induced by doxorubi- cin.This article ispart of a Special Issueentitled:Genetic and epigenetic control of heart failure.