Quercetin ameliorates ferroptosis of rat cardiomyocytes via activation of the SIRT1/p53/SLC7A11 signaling pathway to alleviate sepsis‑induced cardiomyopathy

Sepsis-induced cardiomyopathy (SIC) is a manifestation of multiple organ failure as a result of sepsis and is a serious threat to life. Here, the effect and mechanisms of quercetin (QUE) in SIC were assessed. It was found that patients with SIC expressed lower serum levels of glutathione peroxidase...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular medicine 2023-12, Vol.52 (6), p.1, Article 116
Main Authors: Lin, Xin, Zhao, Xiaoxia, Chen, Qingfeng, Wang, Xiaoyue, Wu, Yongya, Zhao, Hao
Format: Article
Language:English
Subjects:
Abdomen
Apoptosis
Bacterial infections
Biotechnology
Cardiomyocytes
Cardiomyopathy
Cell culture
Cell death
Comparative analysis
Creatine kinase
Cytochrome c
Ferritin
Ferroptosis
Health aspects
Heart cells
Heart diseases
Infection
Inflammation
Kidneys
Laboratory animals
Lipid peroxidation
Lipids
Medical research
Medicine, Experimental
Mortality
Oxidative stress
Peroxidase
Proteins
Sepsis
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sepsis-induced cardiomyopathy (SIC) is a manifestation of multiple organ failure as a result of sepsis and is a serious threat to life. Here, the effect and mechanisms of quercetin (QUE) in SIC were assessed. It was found that patients with SIC expressed lower serum levels of glutathione peroxidase 4 (GPX4) and SIRT1 but higher levels of CK-MB, cTnI, TNF-[alpha], and IL-6 compared with healthy individuals. A dose of 80 [micro]M QUE increased the viability and reduced the ferroptosis of H9C2 cells treated with 1.0 [micro]g/ml LPS in vitro. The administration of QUE decreased the levels of MDA, NADPH, lipid peroxidation and cytoplasmic cytochrome C and upregulated the levels of GSH and TOM 20, thus exerting an anti-oxidative effect via mediating SIRT1 expression. It also activated the SIRT1/p53/SLC7A11 signaling pathway to reduce cellular [Fe.sup.2+] and PTGS2 levels, decreased cell apoptosis rate, and upregulated the levels of GPX4 and ferritin to inhibit ferroptosis of H9C2 cells in vitro. Injection of QUE into rats activated the SIRT1/p53/SLC7A11 signaling pathway, reduced the levels of CK-MB, cTnI, inflammatory cell infiltration, MDA, NADPH, cytoplasmic cytochrome C, cellular [Fe.sup.2+] and PTGS2 but upregulated the levels of GSH, TOM 20, GPX4, and ferritin to alleviate SIC in a dose-dependent manner in vivo. To conclude, QUE exerted an anti-ferroptotic effect via activation of the SIRT1/p53/SLC7A11 signaling pathway to dampen SIC both in vivo and in vitro. These findings highlighted a potential therapeutic strategy for the management of SIC. Key words: quercetin, ferroptosis, cardiomyocytes, SIRT1/p53/SLC7A11 signaling pathway, sepsis-induced cardiomyopathy
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2023.5319