title: Rutin attenuates doxorubicin-induced cardiotoxicity via regulating autophagy and apoptosis.
abstract: 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 activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potential mechanisms of protective effects of rutin against cardiomyocyte death. We analyzed cardiac tissues at the time point of 8weeks after doxorubicin treatment. The results by echocardiography, TUNEL staining, Masson's trichrome staining as well as Western blot analysis revealed that doxorubicin induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were alleviated by rutin treatment. Western blot analysis indicated that the underlying mechanisms included inhibition excessive autophagy and apoptosis mediated by Akt activation. Collectively, our findings suggest that suppression of autophagy and apoptosis by administration of rutin could attenuate doxorubicin-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating this devastating side effect induced by doxorubicin. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Linhe
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Health Sciences, University of Wyoming, Laramie, WY 82071, USA. Electronic address: jren@uwyo.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: yangjian1212@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D054715:Cardiotoxins / Q000009:adverse effects* / Q000494:pharmacology; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D012431:Rutin / Q000494:pharmacology*
chemical_list: D054715:Cardiotoxins; D012431:Rutin; D004317:Doxorubicin
keywords: Apoptosis; Autophagy; Cardiotoxicity; Doxorubicin; Rutin