Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase

Abstract Background Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunc...

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Main Authors: Le Duan, Lini Quan, Bin Zheng, Zhe Li, Guangchao Zhang, Mengdi Zhang, Huacheng Zhou
Format: Article
Language:English
Published: BMC 2023-06-01
Series:BMC Pulmonary Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12890-023-02504-6
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author Le Duan
Lini Quan
Bin Zheng
Zhe Li
Guangchao Zhang
Mengdi Zhang
Huacheng Zhou
author_facet Le Duan
Lini Quan
Bin Zheng
Zhe Li
Guangchao Zhang
Mengdi Zhang
Huacheng Zhou
author_sort Le Duan
collection DOAJ
description Abstract Background Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism. Methods Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed. Results Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group. Conclusions Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.
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spelling doaj.art-e43d4f49c6de4b7faed1f460059822fe2023-06-18T11:05:23ZengBMCBMC Pulmonary Medicine1471-24662023-06-0123111110.1186/s12890-023-02504-6Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phaseLe Duan0Lini Quan1Bin Zheng2Zhe Li3Guangchao Zhang4Mengdi Zhang5Huacheng Zhou6Department of Anesthesiology, the Second Affiliated Hospital of Harbin Medical UniversityDepartment of Anesthesiology, the Second Affiliated Hospital of Harbin Medical UniversityDepartment of Anesthesiology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Anesthesiology, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Anesthesiology, Affiliated Hospital of Nantong UniversityDepartment of Anesthesiology, the Fourth Affiliated Hospital of Harbin Medical UniversityDepartment of Pain Medicine, the Fourth Affiliated Hospital of Harbin Medical UniversityAbstract Background Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism. Methods Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed. Results Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group. Conclusions Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.https://doi.org/10.1186/s12890-023-02504-6HydrogenLung transplantationMitochondrial functionDonor lung qualityCold ischemiaInflammation
spellingShingle Le Duan
Lini Quan
Bin Zheng
Zhe Li
Guangchao Zhang
Mengdi Zhang
Huacheng Zhou
Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
BMC Pulmonary Medicine
Hydrogen
Lung transplantation
Mitochondrial function
Donor lung quality
Cold ischemia
Inflammation
title Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
title_full Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
title_fullStr Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
title_full_unstemmed Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
title_short Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
title_sort inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase
topic Hydrogen
Lung transplantation
Mitochondrial function
Donor lung quality
Cold ischemia
Inflammation
url https://doi.org/10.1186/s12890-023-02504-6
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