High concentration of hydrogen gas alleviates Lipopolysaccharide-induced lung injury via activating Nrf2 signaling pathway in mice

Guolin Wang, Jiayan Zhang, Keliang Xie, Nan Zhao, Ruiqiang Sun, Yanchao Su, Yaoqi Wang, Yonghao Yu, Yuzun Wang, Zhen Wang

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DOI: 10.1016/j.intimp.2021.108198 DOI is the universal ID for this study.

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Background and aims: The lung is the first organ to fail in sepsis. Our previous studies have proven that 2% molecular hydrogen (H2) inhalation remain a protective effect on a septic animal model via its anti-inflammatory and anti-apoptosis properties. This current research aims to observe the therapeutic effect of high concentration hydrogen (67%, HCH) on lipopolysaccharide (LPS) induced acute lung injury (ALI), and further investgate the role of Nrf2 signaling pathway.

Methods: ALI model was induced by LPS areosol inhalation. HCH were treated for 1 h at 1 and 6 h after modelling. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 4 and 24 h after the exposure of LPS. The histological scores, wet/dry weight ratios, myeloperoxidase (MPO) activity, protein content and cytokine levels in BALF, apoptosis condition of lung cells, expression of Nrf2 and NF-κB were assessed in both wild type and Nrf2-knockout mice.

Results: HCH Inhalation significantly alleviated LPS-induced pathological alterations of lung, and reduced the protein concentration, the wet/dry weight ratio, and the MPO activity of lung tissue. HCH Inhalation improved LPS-induced increasement in caspase-3 activity and the number of TUNEL-positive cells. HCH inhalation attenuated the LPS induced increased total cell content and polymorphonuclear granulocyte content, and pro-inflammatory cytokines, Nrf2 and NF-κB expression. HCH could not produce protective effct in Nrf2-knockout mice.

Conclusion: HCH can effectively alleviate LPS-induced ALI, which may be related to activation of Nrf2 signaling pathway and inhibition of inflammatory response and cell apoptosis mediated by NF-κB.

Publish Year 2021
Country China
Rank Positive
Journal International Immunopharmacology
Primary Topic Lung
Secondary TopicSepsis
Model Mouse
Tertiary TopicLung Injury
Vehicle Gas
pH N/A
Application Inhalation