Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro.
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.
Liu
Zhe
Z
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.
Song
Xiao-dong
XD
Xin
Ying
Y
Wang
Xiao-jian
XJ
Yu
Hui
H
Bai
Yong-yi
YY
Liu
Jun-hao
JH
Zhang
Chan-na
CN
Hui
Ru-tai
RT
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
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