Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ

Abstract

Cardiotoxicity limits the clinical applications of doxorubicin (Dox), which mechanism might be excess generation of intracellular ROS. Quercetin (Que) is a flavonoid that possesses anti-oxidative activities, exerts myocardial protection. We hypothesized that the cardioprotection against Dox injury of Que involved 14-3-3γ, and mitochondria. To investigate the hypothesis, we treated primary cardiomyocytes with Dox and determined the effects of Que pretreatment with or without 14-3-3γ knockdown. We analyzed various cellular and molecular indexes. Our data showed that Que attenuated Dox-induced toxicity in cardiomyocytes by upregulating 14-3-3γ expression. Que pretreatment increased cell viability, SOD, catalase, and GPx activities, GSH levels, MMP and the GSH/GSSG ratio; decreased LDH and caspase-3 activities, MDA and ROS levels, mPTP opening and the percentage of apoptotic cells. However, Que’s cardioprotection were attenuated by knocking down 14-3-3γ expression using pAD/14-3-3γ-shRNA. In conclusion, Que protects cardiomyocytes against Dox injury by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ.

Keywords:

• Quercetin
• doxorubicin
• 14-3-3γ
• cardiotoxicity
• oxidative stress
• mitochondria

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by the grants from the Natural Science Foundation of China [No: 81803534 and 81660538], and the Natural Scientific Foundation of Jiangxi province [No: 20171BAB215077].