Alanyl-glutamine-supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats.
BACKGROUND
Intestinal ischemia-reperfusion (I/R) injury plays an important role in the pathogenesis of systemic inflammation and multiple-organ failure. We studied whether glutamine, the primary fuel of the small intestine, prevents intestinal mucosal damage after intestinal I/R in rats.


METHODS
Rats were randomly divided into 4 groups: a sham-standard amino acid (SAA) group (n = 8); a sham-glutamine (Gln) group (n = 8); an I/R-SAA group (n = 10); and an I/R-Gln group (n = 9). Alanyl-glutamine solution was produced by replacing 36% of the total amino acid nitrogen with Gln. The superior mesenteric artery was ligated. After 60 minutes of ischemia, reperfusion was initiated and infusion was started. After 24-hour reperfusion, the intestinal segment was removed for morphological and biochemical analysis, and blood samples were drawn from the portal vein. Fluorescein isothiocyanate-conjugated dextran 70,000 (FITC-dextran) was infused into the duodenum 2 hours before animal death.


RESULTS
In the I/R-SAA group, extensive epithelial sloughing and mucosal ulceration of villous tips were observed, whereas these findings did not occur in the I/R-Gln group. Mucosal wet weight, DNA, and protein content decreased significantly in the I/R-SAA group compared with the sham-SAA group and increased significantly in the I/R-Gln group compared with the I/R-SAA group. Plasma FITC-dextran significantly increased in the I/R-SAA group compared with the sham-SAA group, but the plasma level in the I/R-Gln group was comparable with that of each sham group. Mucosal glutaminase activity significantly increased in both the I/R-SAA and I/R-Gln groups compared with the sham-SAA and sham-Gln groups, respectively.


CONCLUSIONS
Alanyl-glutamine protects against morphologic and functional mucosal injury after intestinal I/R in rats.
Tazuke
Yuko
Y
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Wasa
Masafumi
M
Shimizu
Yoshiyuki
Y
Wang
Hong-Sheng
HS
Okada
Akira
A
D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage* / Q000494:pharmacology; D005972:Glutaminase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010288:Parenteral Nutrition; D010539:Permeability / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D004151:Dipeptides; D005972:Glutaminase; C054122:alanylglutamine