Edaravone protects H9 c2 cells against doxorubicin-induced cardiotoxicity
10.3969/j.issn.1001-1978.2014.04.011
- VernacularTitle:依达拉奉保护H9 c2心肌细胞对抗阿霉素的心肌毒性作用
- Author:
Guangjiao LIU
;
Runmin GUO
;
Wenming XU
;
Ning SHEN
;
Jianqiang FENG
;
Xinxue LIAO
- Publication Type:Journal Article
- Keywords:
edaravone;
doxorubicin;
cardiotoxicity;
reactive oxygen species;
apoptosis;
mitochondrial membrance potential
- From:
Chinese Pharmacological Bulletin
2014;(4):490-495
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore whether edaravone (EDA), a novel free radical scavenger, protects H9c2 cardiac cells against doxorubicin ( DOX )-induced car-diotoxicity. Methods H9c2 cells were treated with 5μmol·L-1 DOX to establish a model of DOX cardio-toxicity. Cell viability was examined by cell counter kit ( CCK-8 ) . Changes in morphology and amount of ap-optotic cells were detected by Hoechst 33258 staining;intracellular level of reactive oxygen species ( ROS ) was measured by DCFH-DA staining and photofluorog-raphy;mitochondrial membrane potential ( MMP) was observed by rhodamine 123 ( RH123 ) staining and photoflurograph; the expression level of caspase-3 was determined by Western blot assay. Results Pretreat-ment of H9 c2 cells with 20 , 40 and 80 μmol · L-1 EDA for 60 min markedly inhibited cytotoxicity in-duced by 5 μmol · L-1 DOX, respectively, as evi-denced by an increase in cell viability. The protective effect induced by 40 μmol · L-1 EDA was maximal. Pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 30 , 60 , 90 and 120 min significantly attenuated DOX-induced cytotoxicity, respectively, having a max-imal protection at 60 min. Furthermore, pretreatment of H9 c2 cells with 40 μmol · L-1 EDA for 60 min be-fore exposure to 5 μmol · L-1 DOX for 24 h obviously reduced cardiac injuries, as evidenced by decreases in the DOX-induced intracellular ROS generation, num-ber of apoptotic cells, and expression of cleaved caspase-3, as well as loss of MMP. Conclusions EDA can protect H9 c2 cardiac cells against DOX-in-duced cardiotoxicity, this protection may be associated with inhibition of ROS production and preservation of MMP.
