title: Hydrogen sulfide prevents hyperoxia-induced lung injury by downregulating reactive oxygen species formation and angiopoietin-2 release.
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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Faller
authors.forename: Sashko G
authors.initials: SG
authors.lastname: Spassov
authors.forename: Kornelia K
authors.initials: KK
authors.lastname: Zimmermann
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Buerkle
authors.forename: Torsten
authors.initials: T
authors.lastname: Loop
authors.forename: Rene
authors.initials: R
authors.lastname: Schmidt
authors.forename: Karl M
authors.initials: KM
authors.lastname: Strosing
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoetzel
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D018496:Hyperoxia / Q000150:complications*; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D042702:Angiopoietin-2; D017382:Reactive Oxygen Species; D006862:Hydrogen Sulfide