title: Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro.
abstract: BACKGROUND
  The use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. Reactive oxygen species (ROSs) play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.
  
  
  METHODS
  We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst33258 staining and measurement of lactate dehydrogenase (LDH) release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay.
  
  
  RESULTS
  The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 microg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.
  
  
  CONCLUSIONS
  Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.
authors: Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, Cardiovascular Institute & Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
authors: Zhe
authors: Z
authors: Liu
authors: Xiao-dong
authors: XD
authors: Song
authors: Ying
authors: Y
authors: Xin
authors: Xiao-jian
authors: XJ
authors: Wang
authors: Hui
authors: H
authors: Yu
authors: Yong-yi
authors: YY
authors: Bai
authors: Jun-hao
authors: JH
authors: Liu
authors: Chan-na
authors: CN
authors: Zhang
authors: Ru-tai
authors: RT
authors: Hui
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D047309:Flavones; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006367:HeLa Cells; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D047309:Flavones; D005419:Flavonoids; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C007054:chrysoeriol