title: Exogenous hydrogen sulfide (H2S) protects alveolar growth in experimental O2-induced neonatal lung injury.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S), carbon monoxide and nitric oxide (NO), belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD.
  
  
  METHODS
  We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) to study its lung protective potential in vitro and in vivo.
  
  
  RESULTS
  In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation.
  
  
  CONCLUSIONS
  H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.
authors.affiliation: Ottawa Hospital Research Institute, Sprott Center for Stem Cell Research, Regenerative Medicine Program and Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Arul
authors.initials: A
authors.lastname: Vadivel
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Alphonse
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Ionescu
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Desiree S
authors.initials: DS
authors.lastname: Machado
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: O'Reilly
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Farah
authors.initials: F
authors.lastname: Eaton
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Al
authors.initials: A
authors.lastname: Haromy
authors.affiliation: Department of Pediatrics, School of Human Development, Women and Children's Health Research Institute, Cardiovascular Research Center and Pulmonary Research Group, University of Alberta, Edmonton, Canada.
authors.forename: Evangelos D
authors.initials: ED
authors.lastname: Michelakis
authors.affiliation: Ottawa Hospital Research Institute, Sprott Center for Stem Cell Research, Regenerative Medicine Program and Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thébaud
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D018496:Hyperoxia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000009:adverse effects; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D011355:Prodrugs; D020011:Protective Agents; D017382:Reactive Oxygen Species; D010100:Oxygen; D006862:Hydrogen Sulfide