title: Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro.
abstract: Doxorubicin (Dox) is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. Isorhamnetin is a nature antioxidant with obvious cardiac protective effect. The aim of this study is going to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p.) administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity. Daily pretreatment with isorhamnetin (5 mg/kg, i.p.) for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. A further mechanism study indicated that isorhamnetin pretreatment can counteract Dox-induced oxidative stress and suppress the activation of mitochondrion apoptotic pathway and mitogen-activated protein kinase pathway. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.forename: Xiangbao
authors.initials: X
authors.lastname: Meng
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.forename: Meng
authors.initials: M
authors.lastname: Qin
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Dayong
authors.initials: D
authors.lastname: Cai
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C047368:3-methylquercetin; D004317:Doxorubicin; D011794:Quercetin; D007770:L-Lactate Dehydrogenase