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Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury

  • Authors:
    • Chunyan Wang
    • Wenlin Yuan
    • Anmin Hu
    • Juan Lin
    • Zhengyuan Xia
    • Catherine F. Yang
    • Yalan Li
    • Zhongjun Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Shenzhen People's Hospital and Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518000, P.R. China, Department of Anesthesiology, The University of Hong Kong, Hong Kong, SAR, P.R. China, Department of Basic Sciences, College of Medicine, CA Northstate University, Elk Grove, CA 60009, USA, Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 175-184
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    Published online on: May 4, 2020
       https://doi.org/10.3892/mmr.2020.11114
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Abstract

Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a α2‑adrenergic receptor (α2‑AR) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YOH), an α2‑AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin‑I (TN‑I), interleukin 6 (IL‑6), superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels, and iron release. Ferroptosis‑targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN‑I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of MDA, 8‑hydroxy‑2'‑deoxyguanosine and the inflammatory factors IL‑6 and monocyte chemoattractant protein‑1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, CLP increased expression levels of heme oxygenase‑1 (HO‑1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of Dex (CLP + Dex + YOH vs. CLP + Dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis‑induced HO‑1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis‑induced myocardial cellular injury.
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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Yuan W, Hu A, Lin J, Xia Z, Yang C , Li Y and Zhang Z: Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury. Mol Med Rep 22: 175-184, 2020.
APA
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. . ... Zhang, Z. (2020). Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury. Molecular Medicine Reports, 22, 175-184. https://doi.org/10.3892/mmr.2020.11114
MLA
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. ., Li, Y., Zhang, Z."Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury". Molecular Medicine Reports 22.1 (2020): 175-184.
Chicago
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. ., Li, Y., Zhang, Z."Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury". Molecular Medicine Reports 22, no. 1 (2020): 175-184. https://doi.org/10.3892/mmr.2020.11114
Copy and paste a formatted citation
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Spandidos Publications style
Wang C, Yuan W, Hu A, Lin J, Xia Z, Yang C , Li Y and Zhang Z: Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury. Mol Med Rep 22: 175-184, 2020.
APA
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. . ... Zhang, Z. (2020). Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury. Molecular Medicine Reports, 22, 175-184. https://doi.org/10.3892/mmr.2020.11114
MLA
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. ., Li, Y., Zhang, Z."Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury". Molecular Medicine Reports 22.1 (2020): 175-184.
Chicago
Wang, C., Yuan, W., Hu, A., Lin, J., Xia, Z., Yang, C. ., Li, Y., Zhang, Z."Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury". Molecular Medicine Reports 22, no. 1 (2020): 175-184. https://doi.org/10.3892/mmr.2020.11114
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