L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes.
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.
Haynes
Tony E
TE
Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
Li
Peng
P
Li
Xilong
X
Shimotori
Kazuhiro
K
Sato
Hiroyuki
H
Flynn
Nick E
NE
Wang
Junjun
J
Knabe
Darrell A
DA
Wu
Guoyao
G
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
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