Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC

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Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC[J]. Journal of Kunming Medical University.

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Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC[J]. Journal of Kunming Medical University.

Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC[J]. Journal of Kunming Medical University.

Citation:

Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC[J]. Journal of Kunming Medical University.

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Quercetin Regulates Mitochondrial Damage and Ferroptosis in Sepsis-induced Cardiomyopathy in Mice and Cardiomyocytes via TFRC

1.
Department of Emergency Medicine
2.
Department of Critical Care Medicine, Yan’an Hospital of Kunming City, Kunming Yunnan 650032, China

Received Date: 2025-12-07

Abstract

Abstract

Objective To investigate the effects of quercetin （QUE） on regulating transferrin receptor （TFRC） expression on mitochondrial function and ferroptosis in a sepsis-induced cardiomyopathy （SCM） cell model, and to elucidate the underlying regulatory mechanisms. Methods H9C2 cells were treated with 1 μg/mL LPS and co-cultured with 20 μM, 40 μM, 80 μM, or 160 μM QUE for 24 hours. H9C2 Cells treated with 80 μM QUE were transfected with sh-TFRC, pcDNA-TFRC, or treated with the ferroptosis inhibitor Ferrostatin-1 for 24 hours. The regulatory effect of QUE on TFRC expression and the effects of QUE-regulated TFRC regulation on LPS-induced mitochondrial dysfunction and ferroptosis in H9C2 cells were assessed using CCK-8 assay, flow cytometry, JC-1 staining, Western blot, commercial kits, enzyme-linked immunosorbent assay （ELISA）, and RT-qPCR. QUE was intraperitoneally injected into mice and LPS was administered to establish an SCM mouse model. The effects of QUE on SCM mice were investigated using hematoxylin-eosin staining, TUNEL staining, ELISA, commercial kits, and Western blotting. Results LPS stimulation significantly inhibited H9C2 cell proliferation, promoted cell apoptosis, and increased the levels of ROS, cleaved-caspase 3, Bax, FTH1, ACSL4, Fe²⁺, IL-1β, TNF-α, LDH, and CK-MB （P < 0.001）, while decreasing mitochondrial membrane potential and expression of Bcl-2 and glutathione peroxidase 4 （GPX4） proteins （P < 0.001）. Treatment with 40 μM, 80 μM, and 160 μM QUE significantly alleviated LPS-induced mitochondrial dysfunction and ferroptosis in H9C2 cells （all P < 0.05） and inhibited TFRC expression （P < 0.001）. TFRC knockdown or Ferrostatin-1 treatment further enhanced the protective effect of 80 μM QUE against H9C2 cell injury （all P < 0.05）. TFRC overexpression exacerbated LPS-induced mitochondrial dysfunction and ferroptosis in H9C2 cells, while QUE treatment alleviated the effects of TFRC overexpression on H9C2 cells. LPS stimulation increased cardiac myocyte injury and death and elevated inflammatory cytokines levels in SCM mice. QUE treatment mitigated myocardial injury and suppressed ferroptosis in SCM mice. Conclusion QUE alleviates LPS-induced mitochondrial injury in H9C2 cells and cardiac myocardial injury in mice by downregulating TFRC expression and inhibiting ferroptosis.
- Septic cardiomyopathy,
- Quercetin,
- TFRC,
- Mitochondria,
- Ferroptosis

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References(23)

References

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