Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND AND 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 with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model. METHODS: Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P7-P12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P12-P17). Mouse pups received Arg-Gln (5 g·kg· day) or DHA (5 g· kg·day) or vehicle orally started on P12 through P17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated. RESULTS: Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (P <0.05). Arg-Gln dipeptide and DHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (P <0.05). Supplementation of Arg-Gln or DHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (P <0.05). CONCLUSIONS: Supplementation with either Arg-Gln or DHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

Original languageEnglish (US)
Pages (from-to)499-504
Number of pages6
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume54
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Fingerprint

arginyl-glutamine
Hyperoxia
Docosahexaenoic Acids
Dipeptides
Wounds and Injuries
L-Lactate Dehydrogenase
Peroxidase
Small Intestine
Oxygen
Glutamine

Keywords

  • arginine
  • dipeptide
  • docosahexaenoic acid
  • glutamine
  • intestinal injury

ASJC Scopus subject areas

  • Gastroenterology
  • Pediatrics, Perinatology, and Child Health

Cite this

Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice. / Li, Nan; Ma, Liya; Liu, Xueyan; Shaw, Lynn; Calzi, Sergio Li; Grant, Maria B.; Neu, Josef.

In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 54, No. 4, 04.2012, p. 499-504.

Research output: Contribution to journalArticle

Li, Nan ; Ma, Liya ; Liu, Xueyan ; Shaw, Lynn ; Calzi, Sergio Li ; Grant, Maria B. ; Neu, Josef. / Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice. In: Journal of Pediatric Gastroenterology and Nutrition. 2012 ; Vol. 54, No. 4. pp. 499-504.
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T1 - Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice

AU - Li, Nan

AU - Ma, Liya

AU - Liu, Xueyan

AU - Shaw, Lynn

AU - Calzi, Sergio Li

AU - Grant, Maria B.

AU - Neu, Josef

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AB - BACKGROUND AND 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 with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model. METHODS: Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P7-P12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P12-P17). Mouse pups received Arg-Gln (5 g·kg· day) or DHA (5 g· kg·day) or vehicle orally started on P12 through P17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated. RESULTS: Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (P <0.05). Arg-Gln dipeptide and DHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (P <0.05). Supplementation of Arg-Gln or DHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (P <0.05). CONCLUSIONS: Supplementation with either Arg-Gln or DHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

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