Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice

Int Immunopharmacol. 2011 Dec;11(12):2130-7. doi: 10.1016/j.intimp.2011.09.007. Epub 2011 Oct 19.


Acute lung injury (ALI) is a serious illness, the incidence and mortality of which are very high. Free radicals, such as hydroxyl radicals (OH) and peroxynitrite (ONOO(-)), are considered to be the final causative molecules in the pathogenesis of ALI. Hydrogen, a new antioxidant, can selectively reduce OH and ONOO(-). In the present study, we investigated the hypothesis that hydrogen inhalation could ameliorate ALI induced by intra-tracheal lipopolysaccharide (LPS, 5mg/kg body weight). Mice were randomized into three groups: sham group (physiological saline+2% hydrogen mixed gas), control group (LPS+normal air) and experiment group (LPS+2% hydrogen mixed gas). Bronchoalveolar lavage fluid (BALF) was performed to determine the total protein concentrations and pro-inflammatory cytokines. Lung tissues were assayed for oxidative stress variables, wet/dry (W/D) ratio, histological, immunohistochemistry and Western blotting examinations. Our experiments exhibited that hydrogen improved the survival rate of mice and induced a decrease in lung W/D ratio. In addition, hydrogen decreased malonaldehyde and nitrotyrosine content, inhibited myeloperoxidase and maintained superoxide dismutase activity in lung tissues and associated with a decrease in the expression of TNF-α, IL-1β, IL-6 and total protein concentrations in the BALF. Hydrogen further attenuated histopathological alterations and mitigated lung cell apoptosis. Importantly, hydrogen inhibited the activation of P-JNK, and also reversed changes in Bax, Bcl-xl and caspase-3. In conclusion, our data demonstrated that hydrogen inhalation ameliorated LPS-induced ALI and it may be exerting its protective role by preventing the activation of ROS-JNK-caspase-3 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / mortality
  • Acute Lung Injury / pathology
  • Administration, Inhalation
  • Animals
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Caspase 3 / metabolism
  • Cytokines / analysis
  • Hydrogen / administration & dosage*
  • Lipopolysaccharides / administration & dosage
  • MAP Kinase Signaling System / drug effects
  • Male
  • Malondialdehyde / analysis
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • Pulmonary Edema / drug therapy
  • Pulmonary Edema / metabolism
  • Superoxide Dismutase / analysis
  • Treatment Outcome
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / metabolism


  • Antioxidants
  • Bax protein, mouse
  • Cytokines
  • Lipopolysaccharides
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • 3-nitrotyrosine
  • Tyrosine
  • Malondialdehyde
  • Hydrogen
  • Peroxidase
  • Superoxide Dismutase
  • Caspase 3