title: Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice.
abstract: OBJECTIVE
  Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia.
  
  
  METHODS
  Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7-12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12-17). Mouse pups received Arg-Gln (5 g · kg⁻¹ · d⁻¹) or DHA (5 g · kg⁻¹ · d⁻¹) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group.
  
  
  RESULTS
  The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor.
  
  
  CONCLUSIONS
  The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants.
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, Florida, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Ma
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xueyan
authors.initials: X
authors.lastname: Liu
authors.forename: Lynn
authors.initials: L
authors.lastname: Shaw
authors.forename: Sergio
authors.initials: S
authors.lastname: Li Calzi
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.forename: Josef
authors.initials: J
authors.lastname: Neu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001273:Atmosphere Exposure Chambers; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D004151:Dipeptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007774:Lactation; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004151:Dipeptides; D018836:Inflammation Mediators; C578860:arginyl-glutamine; D004281:Docosahexaenoic Acids