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

Liya Ma, Nan Li, Xueyan Liu, Lynn Shaw, Sergio Li Calzi, Maria B. Grant, Josef Neu

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1186-1191
Number of pages6
JournalNutrition
Volume28
Issue number11-12
DOIs
StatePublished - Nov 1 2012

Keywords

  • Arginine
  • Bronchopulmonary dysplasia
  • Dipeptide
  • Docosahexaenoic acid
  • Glutamine
  • Hyperoxia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Ma, L., Li, N., Liu, X., Shaw, L., Li Calzi, S., Grant, M. B., & Neu, J. (2012). Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice. Nutrition, 28(11-12), 1186-1191. https://doi.org/10.1016/j.nut.2012.04.001