title: Amelioration of hyperoxia-induced lung injury using a sphingolipid-based intervention.
abstract: The aim of this study was to characterise lung function and bronchoalveolar lavage sphingolipid profile in newborn mice during hyperoxia exposure and recovery in room air, and to examine the effect of d-sphingosine supplementation during recovery. Newborn mice were exposed to 80% oxygen for 4 weeks and allowed to recover in room air for another 4 weeks. Lung function measurements and morphometrical analysis of lung tissue were performed and bronchoalveolar lavage fluid was collected during hyperoxia and recovery with and without d-sphingosine supplementation. Hyperoxia exposure altered lung function, which partially recovered in room air. Lungs had fewer and enlarged alveoli which persisted during recovery. Multiple sphingolipids were significantly increased after hyperoxia. Ceramides were increased after 2 weeks of recovery, but normalised to control values after 4 weeks. The addition of d-sphingosine during the first 5 days of recovery accelerated the normalisation of ceramide levels at 2 weeks and partially reversed the hyperoxia-induced increase in alveolar size and arrest in alveolarisation at 4 weeks. Exposure of newborn mice to hyperoxia caused restrictive and obstructive lung function changes that partially recovered in room air, while alveolar morphology remained abnormal. Hyperoxia increased ceramide levels, with normalisation after recovery. d-sphingosine addition during recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar arrest.
authors.affiliation: Dept of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Tibboel
authors.forename: Stephen
authors.initials: S
authors.lastname: Joza
authors.forename: Irwin
authors.initials: I
authors.lastname: Reiss
authors.forename: Johan C
authors.initials: JC
authors.lastname: de Jongste
authors.forename: Martin
authors.initials: M
authors.lastname: Post
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001997:Bronchopulmonary Dysplasia / Q000209:etiology; D002518:Ceramides / Q000378:metabolism*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D055370:Lung Injury / Q000378:metabolism* / Q000517:prevention & control; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014797:Vital Capacity
chemical_list: D002518:Ceramides; D013107:Sphingolipids; C109343:dihydroceramide; D013110:Sphingosine; C005682:safingol