PT  - JOURNAL ARTICLE
AU  - Jeroen Tibboel
AU  - Stephen Joza
AU  - Irwin Reiss
AU  - Johan C. de Jongste
AU  - Martin Post
TI  - Amelioration of hyperoxia-induced lung injury in newborn mice using a sphingolipid-based intervention
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3768
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3768.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3768.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Aim: To characterize lung function and BAL sphingolipid profile of newborn mice during hyperoxia exposure and recovery in room air, and to examine the effect of D-sphingosine supplementation during recovery.Methods: Newborn mice were exposed to 80% O2 for 4 weeks and allowed to recover in room air for another 4 weeks. Lung function measurements, histological and morphometrical analysis of lung tissue was performed and BAL fluid was collected during hyperoxia and after recovery with and without D-sphingosine supplementation. Sphingolipids in BAL were quantified by tandem mass spectrometry.Results: Hyperoxia increased lung resistance and decreased compliance, total lung capacity and forced expiratory flow. After recovery, resistance, compliance and total lung capacity had normalized whereas forced flows remained low. Sphingolipids, including ceramides, were significantly increased after hyperoxia. Ceramides were still increased after 2 weeks of recovery, but normalized to control values after 4 weeks. Addition of D-sphingosine during the first 5 days of recovery reduced ceramide levels at 2 weeks and partially reversed the hyperoxia-induced increase in alveolar size and arrest in alveolarization at 4 weeks, although no further improvement in lung function parameters was observed.Conclusion: 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 normalization after recovery. D-sphingosine addition during recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar arrest.