Skip Navigation LinksHome > April 2012 - Volume 54 - Issue 4 > Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuat...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3182330867
Original Articles: Gastroenterology

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*

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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−1 · day−1) or DHA (5 g · kg−1 · day−1) 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.

Copyright 2012 by ESPGHAN and NASPGHAN


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