Quercetin protects cardiomyocytes against doxorubicin induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14 3 3g
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 3g, and mitochondria. To investigate the hypothesis, we treated primary cardiomyocytes with Dox and determined the effects of Que pretreatment with or without 14 3 3g knockdown. We analyzed various cellular and molecular indexes. Our data showed that Que attenuated Dox induced toxicity in cardiomyocytes by upregulating 14 3 3g 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 3g expression using pAD/14 3 3g shRNA. In conclusion, Que protects cardiomyocytes against Dox injury by suppressing oxidative stress and improving mitochondrial function via 14 3 3g.
Toxicology mechanisms and methods