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Methylene Blue Protects the Isolated Rat Lungs from Ischemia–Reperfusion Injury by Attenuating Mitochondrial Oxidative Damage

  • Acute Lung Injury
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Abstract

Introduction

Impaired mitochondrial function is a key factor attributing to the lung ischemia reperfusion injury (LIRI). Methylene blue (MB) has been reported to attenuate brain and renal ischemia–reperfusion injury. We hypothesized that MB also could have a protective effect against LIRI by preventing mitochondrial oxidative damage.

Methods

Isolated rat lungs were assigned to the following four groups (n = 6): a sham group: perfusion for 105 min without ischemia; I/R group: shutoff of perfusion and ventilation for 45 min followed by reperfusion for 60 min; and I/R + MB group and I/R + glutathione (GSH) group: 2 mg/kg MB or 4 μM glutathione were intraperitoneally administered for 2 h, and followed by 45 min of ischemia and 60 min of reperfusion.

Results

MB lessened pulmonary dysfunction and severe histological injury induced by ischemia–reperfusion injury. MB reduced the production of reactive oxygen species and malondialdehyde and enhanced the activity of superoxide dismutase. MB also suppressed the opening of the mitochondrial permeability transition pore and partly preserved mitochondrial membrane potential. Moreover, MB inhibited the release of cytochrome c from the mitochondria into the cytosol and decreased apoptosis. Additionally, MB downregulated the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18).

Conclusion

MB protects the isolated rat lungs against ischemia–reperfusion injury by attenuating mitochondrial damage.

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Funding

This work was supported by the following Grants: National Natural Science Foundation of China (81270126); Fundamental Research Funds for the Central Universities (JUSRP51412B); The Science Funds for Health and Family Planning Commission of Sichuan Province (150234); Jiangsu Province Natural Science Foundation (BK20161141); and Graduate Student Research Innovation Project (KYZZ16_0312, KYLX15_1196).

Author information

Author notes

  1. Wen-fang Tian, Si Zeng, and Jun-liang Chen have contributed equally to this work.

Authors and Affiliations

  1. Wuxi School of Medicine, Jiangnan University, No.1800 Lihu Road, 214122, Wuxi, China

    Wen-fang Tian, Qiong Sheng, Jun-liang Chen, Ping Weng, Xiao-tong Zhang, Jia-jia Yuan & Qing-feng Pang

  2. Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, China

    Si Zeng

  3. Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Jiangnan University, No. 200, Huihe Road, 214062, Wuxi, China

    Zhi-qiang Wang

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  1. Wen-fang Tian
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Correspondence to Qing-feng Pang or Zhi-qiang Wang.

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The authors declare that they have no conflict of interest.

Ethical Approval

This research involved rats. The study was approved by the Animal Care and Use Committee of Jiangnan University.

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Tian, Wf., Zeng, S., Sheng, Q. et al. Methylene Blue Protects the Isolated Rat Lungs from Ischemia–Reperfusion Injury by Attenuating Mitochondrial Oxidative Damage. Lung 196, 73–82 (2018). https://doi.org/10.1007/s00408-017-0072-8

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