title: L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes.
abstract: This study tested the hypothesis that L-glutamine (Gln) or L-alanyl-L-glutamine (Ala-Gln) prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Enterocytes of neonatal pigs rapidly hydrolyzed Ala-Gln and utilized Gln. To determine whether Gln or Ala-Gln has a cytoprotective effect, IPEC-1 cells were cultured for 24 h in Gln-free Dulbecco's modified Eagle's-F12 Ham medium containing 0, 0.5, 2.0 or 5.0 mM Gln or Ala-Gln, and 0, 0.5 mM H(2)O(2) or 30 ng/ml lipopolysaccharide (LPS). Without Gln or Ala-Gln, H(2)O(2)- or LPS-treated cells exhibited almost complete death. Gln or Ala-Gln at 0.5, 2 and 5 mM dose-dependently reduced H(2)O(2)- or LPS-induced cell death by 14, 54 and 95%, respectively, whereas D: -glutamine, alanine, glutamate, ornithine, proline, glucosamine or nucleosides had no effect. To evaluate the effectiveness of Gln or Ala-Gln in vivo, 7-day-old piglets received one-week oral administration of Gln or Ala-Gln (3.42 mmol/kg body weight) twice daily and then a single intraperitoneal injection of LPS (0.1 mg/kg body weight); piglets were euthanized in 24 and 48 h to analyze intestinal apoptotic proteins and morphology. Administration of Gln or Ala-Gln to LPS-challenged piglets increased Gln concentrations in small-intestinal lumen and plasma, reduced intestinal expression of Toll-like receptor-4, active caspase-3 and NFkB, ameliorated intestinal injury, decreased rectal temperature, and enhanced growth performance. These results demonstrate a protective effect of Gln or Ala-Gln against H(2)O(2)- or LPS-induced enterocyte death. The findings support addition of Gln or Ala-Gln to current Gln-free pediatric amino acid solutions to prevent intestinal oxidative injury and inflammatory disease in neonates.
authors.affiliation: Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Tony E
authors.initials: TE
authors.lastname: Haynes
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimotori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Nick E
authors.initials: NE
authors.lastname: Flynn
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.forename: Darrell A
authors.initials: DA
authors.lastname: Knabe
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004151:Dipeptides / Q000494:pharmacology*; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008892:Milk / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D013552:Swine / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D004151:Dipeptides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D016877:Oxidants; D051197:Toll-Like Receptor 4; D005973:Glutamine; D006861:Hydrogen Peroxide; D053148:Caspase 3; C054122:alanylglutamine