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The Dipeptide Alanyl-Glutamine Prevents Intestinal Mucosal Atrophy in Parenterally Fed Rats

Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan

Rchiro Nezu, MD

First Department of Surgery, Osaka University Medical School, Osaka, Japan

Ikuo Imamura, PHARMD

Department of Pharmacology , Osaka University Medical School, Osaka, Japan

Yoshinobu Matsuo, MD

Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan

Yoji Takagi, MD, PHD

Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan

Shinkichi Kamata, MD, PHD

Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan

Akira Okada, MD, PHD

Department of Pediatric Surgery, Osaka University Medical School, Osaka, Japan

This study was performed to determine whether the addition of alanyl-glutamine (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing 250 g were randomly divided into four groups: group I was killed after overnight fasting; group II received S-TPN. The other groups received S-TPN supplemented with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2 g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1 week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small bowel, and distal ileum were obtained for morphologic and functional analysis.

Weight gain did not differ significantly among these four groups, and there was no difference in nitrogen balance between groups III and IV. Serum glutamine in group IV (102.8 ± 13.3 µmol/dL) was significantly increased (p < .05) compared with groups I, II, and III (66.2 ± 3.9, 55.7 ± 7.8, and 61.3 ± 10.8 µmol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and maltase of group IV were significantly increased (p < .05) compared with groups II and III. Villus height was significantly increased (p < .05) in the jejunum of group IV rats compared with groups II and III, but not in any other segments of the intestine. No significant changes were observed in crypt depth among all groups. Diamine oxidase in groups II, III, and IV was significantly decreased (p < .05) compared with group I in all segments except for the ileum. Significant decreases (p < .05) in mucosal weight, RNA content, maltase, sucrase, and diamine oxidase activity were observed in groups II and III compared with group I. These results provide further evidence that administration of S-TPN solution results in significant mucosal atrophy. The results also indicate that the specific addition of Ala-Gln to S-TPN may preserve or enhance intestinal mucosal cellularity and function. Thus, alanyl-glutamine, the stable form of glutamine, may be a suitable form for inclusion in TPN formulas. (Journal of Parenteral and Enteral Nutrition 16:110-116, 1992)

Journal of Parenteral and Enteral Nutrition, Vol. 16, No. 2, 110-116 (1992)
DOI: 10.1177/0148607192016002110


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