Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro.
- Author:
Zhe LIU
1
;
Xiao-dong SONG
;
Ying XIN
;
Xiao-jian WANG
;
Hui YU
;
Yong-yi BAI
;
Jun-hao LIU
;
Chan-na ZHANG
;
Ru-tai HUI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antibiotics, Antineoplastic; pharmacology; Cell Line; Cell Survival; drug effects; Doxorubicin; pharmacology; Flavones; Flavonoids; chemistry; pharmacology; Glutathione Peroxidase; metabolism; HeLa Cells; Heart; drug effects; Humans; L-Lactate Dehydrogenase; metabolism; Molecular Structure; Myocytes, Cardiac; drug effects; Rats; Reactive Oxygen Species; metabolism; Superoxide Dismutase; metabolism
- From: Chinese Medical Journal 2009;122(21):2652-2656
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDThe 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.
METHODSWe 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.
RESULTSThe 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.
CONCLUSIONChrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.