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Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ
- Publication Year :
- 2019
- Publisher :
- Taylor & Francis, 2019.
-
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.
- Subjects :
- Health, Toxicology and Mutagenesis
Apoptosis
010501 environmental sciences
Mitochondrion
Pharmacology
Toxicology
medicine.disease_cause
Mitochondrial Membrane Transport Proteins
01 natural sciences
Antioxidants
Mitochondria, Heart
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
medicine
Animals
Myocytes, Cardiac
Viability assay
Cells, Cultured
0105 earth and related environmental sciences
Membrane Potential, Mitochondrial
Cardioprotection
0303 health sciences
Mitochondrial Permeability Transition Pore
Chemistry
030302 biochemistry & molecular biology
Glutathione
Oxidative Stress
14-3-3 Proteins
Doxorubicin
Gene Knockdown Techniques
Toxicity
Quercetin
Reactive Oxygen Species
Intracellular
Oxidative stress
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6f3d4f6485660dfb4974deee7f9d883b
- Full Text :
- https://doi.org/10.6084/m9.figshare.7731659.v1