Hydrogen Sulfide Prevents Hyperoxia-induced Lung Injury by Downregulating Reactive Oxygen Species Formation and Angiopoietin-2 Release

Author(s): Simone Faller, Sashko G. Spassov, Kornelia K. Zimmermann, Stefan W. Ryter, Hartmut Buerkle, Torsten Loop, Rene Schmidt, Karl M. Strosing, Alexander Hoetzel

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 15 , 2013

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Abstract:

Oxygen therapy is a life-sustaining treatment for patients with respiratory failure. However, prolonged exposure to high oxygen concentrations often results in hyperoxia-induced acute lung injury (HALI). At present, no effective therapeutic intervention can attenuate the development of HALI. In the present study, we investigated whether hydrogen sulfide (H2S) can confer lung protection in a mouse model of HALI. C57BL/6 mice were either exposed to room air or 90 vol% oxygen and received either the H2S donor sodium hydrosulfide (NaHS, 10 mg/kg) or vehicle. Lung injury was assessed by an HALI score in tissue sections. Bronchoalveolar lavage fluid was analyzed for protein content and cellular infiltration. Reactive oxygen species (ROS) were detected by dihydroethidium staining. Angiopoietin- 2 was detected by Western Blotting. Pulmonary epithelial, endothelial, and macrophage cells were stimulated to produce ROS either in the absence or presence of NaHS. Mice exposed to hyperoxia developed substantial lung injury, characterized by an elevated HALI score, cellular infiltration, protein leakage, ROS production, and overexpression of angiopoietin-2. NaHS treatment abolished morphological indices of HALI. Angiopoietin-2 expression was significantly reduced by NaHS in vivo. In endothelial cells and macrophages, angiopoietin-2 was released due to ROS formation and decreased in the presence of NaHS. In conclusion, H2S protects from HALI by preventing ROS production and angiopoietin-2 release.

Keywords: Hydrogen sulfide, hyperoxia induced acute lung injury, reactive oxygen species, angiopoietin-2, organ protection, hyperoxia

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Article Details

VOLUME: 19
ISSUE: 15
Year: 2013
Published on: 20 March, 2013
Page: [2715 - 2721]
Pages: 7
DOI: 10.2174/1381612811319150006
Price: $65

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