Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice

Nutrition. Nov-Dec 2012;28(11-12):1186-91. doi: 10.1016/j.nut.2012.04.001.


Objectives: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Atmosphere Exposure Chambers
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Bronchopulmonary Dysplasia / etiology
  • Bronchopulmonary Dysplasia / metabolism
  • Bronchopulmonary Dysplasia / pathology
  • Bronchopulmonary Dysplasia / prevention & control*
  • Cytokines / blood
  • Cytokines / metabolism
  • Dietary Supplements*
  • Dipeptides / therapeutic use*
  • Disease Models, Animal*
  • Docosahexaenoic Acids / therapeutic use*
  • Female
  • Humans
  • Hyperoxia / physiopathology*
  • Infant, Newborn
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Lactation
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL


  • Biomarkers
  • Cytokines
  • Dipeptides
  • Inflammation Mediators
  • arginyl-glutamine
  • Docosahexaenoic Acids