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Protective Effect of Sevoflurane Preconditioning on Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Modulating Iron Homeostasis and Ferroptosis

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Abstract

To investigate the mechanism whereby sevoflurane (Sev) protects cardiomyocytes from hypoxia/reoxygenation (H/R) injury. The rat cardiomyocyte line H9C2 was exposed to hypoxia (1% oxygen) for 24 h, followed by reoxygenation for 2 h to construct a model of H/R injury. H9C2 was exposed to 2.4% Sev for 45 min before creating a hypoxic environment to observe the effect of Sev. MTT was taken to assess the viability of each group of cells, flow cytometry to detect cell apoptosis, and qRT-PCR or western blot to detect the expression of iron metabolism-related proteins and apoptosis-related proteins in the cells. And the kit determined the levels of total Fe and Fe2+ as well as factors related to oxidative stress in the cells. Administration of Sev significantly increased the cell viability of the H/R group while decreasing the expression of apoptosis-related proteins (Bax, cleaved caspase-3). Ferroportin 1 and mitochondrial ferritin, which are associated with iron metabolism, were considerably up-regulated by Sev, while iron regulatory protein 1, divalent metal transporter 1, and transferrin receptor 1 were significantly down-regulated in H/R cells. Additionally, Sev substantially reduced the levels of total Fe and Fe2+, reactive oxygen species, malondialdehyde, and 4-hydroxynonenal in H/R cells. In conclusion, Sev relieves H/R-induced cardiomyocyte injury by regulating iron homeostasis and ferroptosis.

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Authors and Affiliations

  1. Department of Anesthesia and Perioperative Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China

    Hongguang Sheng, Jun Xiong & Danying Yang

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  1. Hongguang Sheng
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  2. Jun Xiong
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  3. Danying Yang
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Contributions

HS: Conceptualization, data analysis, reviewing final form for submission. JX: Conceptualization, Methodology, Data curation. DY: Methodology, Original draft preparation.

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Correspondence to Hongguang Sheng.

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The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Sheng, H., Xiong, J. & Yang, D. Protective Effect of Sevoflurane Preconditioning on Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Modulating Iron Homeostasis and Ferroptosis. Cardiovasc Toxicol 23, 86–92 (2023). https://doi.org/10.1007/s12012-023-09782-w

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  • DOI: https://doi.org/10.1007/s12012-023-09782-w

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