Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Tomohiro Kawamura, Nobunao Wakabayashi, Norihisa Shigemura, Chien Sheng Huang, Kosuke Masutani, Yugo Tanaka, Kentaro Noda, Ximei Peng, Toru Takahashi, Timothy R. Billiar, Meinoshin Okumura, Yoshiya Toyoda, Thomas W. Kensler, Atsunori Nakao

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume304
Issue number10
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Lung Injury
Hydrogen
Gases
Heme Oxygenase-1
Hyperoxia
Oxygen
Nitrogen
NF-E2-Related Factor 2
Air
Blood Gas Analysis
Critical Care
Critical Illness
Lung Diseases
Genes
Medicine
Transplants
Lung

Keywords

  • Heme oxygenase
  • Hydrogen
  • Inflammation
  • NF-E2-related factor 2

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. / Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.; Nakao, Atsunori.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 304, No. 10, 2013.

Research output: Contribution to journalArticle

Kawamura, T, Wakabayashi, N, Shigemura, N, Huang, CS, Masutani, K, Tanaka, Y, Noda, K, Peng, X, Takahashi, T, Billiar, TR, Okumura, M, Toyoda, Y, Kensler, TW & Nakao, A 2013, 'Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 304, no. 10. https://doi.org/10.1152/ajplung.00164.2012
Kawamura, Tomohiro ; Wakabayashi, Nobunao ; Shigemura, Norihisa ; Huang, Chien Sheng ; Masutani, Kosuke ; Tanaka, Yugo ; Noda, Kentaro ; Peng, Ximei ; Takahashi, Toru ; Billiar, Timothy R. ; Okumura, Meinoshin ; Toyoda, Yoshiya ; Kensler, Thomas W. ; Nakao, Atsunori. / Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2013 ; Vol. 304, No. 10.
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