H2 gas reduces lung injury by activating Nrf2 pathwayScientific Research

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


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

DOI: 10.1016/j.intimp.2021.108198



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.