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    26 views5 pages

    Effect of Glutamine Supplemented Elemental Diet On.5

    Uploaded by

    Claudia Cárdenas

    Copyright:

    © All Rights Reserved
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    Sone of Pedic Gastroenterology and Natron BG ST Spine Kae hc dln Effect of Glutamine-Supplemented Elemental Diet on Mucosal Adaptation following Bowel Resection in Rats Sonia Michail, Hamid Mohammadpour, Jung H. Y. Park, and Jon A. Vanderhoof Department of Pediatvies, University of NebraskaiCreighton University, Omaha, Nebraska, U.S.A ‘Summary: Glutamine is the major fuel for enterocytes and prevents mucosal atrophy in certain animal models, Previous studies in our laboratory have failed (0 show a trophic effect of glutamine on the small-bowel mucosa following massive resection when added to a chow dict However, the complexity of the chow diet might poten- fially interfere with the adequate evaluation ofthe trophic elfect of u single agent such as hutamine. This study was, therefore designed to determine whether the addition of glutamine to an elemental dict would augment mucosal adaptation following massive small intestinal resection in ‘rat model. Male Sprazue-Duvsley rats were divided into two dietary groups, one receiving an amino acid-based pediatric elemental diet supplemented with 22% glutamine, and the other receiving the diet supplemented with 22 Following massive small-bowel resection, the small intestine functionally acapts to inereused nu tvient needs through increasing its slbsorptive sur- face area and subsequently its functional capacity (1). Several factors regulate this intestinal epithelial proliferation, Enteral nutrition plays an important role in stimutating adaptation following resection and regeneration of the damaged mucosa following injury (2.3) Glutamine is @ nonessential amino acid that acts as an important respiratory fuel for enterocytes (4,5). ts addition to parenteral nutrition it has been shown to protect against atrophy of the intestinal mucosa (6) After small bowel resection, there isan increase in gut ghitamine utilization (7). It would ‘Aaddress correspondence and reprint requests to Dr. Jon A. Vanderhoot, Toint Section of Pediatric Grstracnteroogy si Nuteition, 8800 Dodge Street, Suite 330, Oma, NE SRILA, USA ‘Manuscript received November 16, 19%; revision received Jury TR, 1998; accepted January 18, 1995, 394 tlucose. One half of the animals in ench dietary group received 80% jejunoileal resection, and the remainder were sham operated. Fifteen days postsurgery, mucosal weight, DNA, protein, and sucrase activities were deter- ‘mined in both the proxival and the distal small intestine. While both groups of resected snimals developed marked increases in all parameters of adaptation, the elutaming supplemented group did not differ from the control diet sroup in any parameter. The addition of glutamine to an ‘elemental diet had no enhancing effect on intestinal ad- aptation after bowel resection. These results are similar 1o those previously observed in our laboratory when ght ‘amine was added to chow diet. The addition of glutamine {0 an elemental dict cannot be justified on the basis of its, trophic effect in animals therefore seem reasonable to hypothesize that glu- tamine would have an enhancing trophic effect on sinall intestinal adaptation, However, previous studies in our laboratory have failed to demonstrate a trophic effect of pharmacological doses of dietary glutamine in a rat animal model when added to chow diet. It is possible that the complexity of the rat chow diet might have potentially interfered with the adequate evaluation of the trophic effect of a single agent such as glutamine (8). This study was therefore designed to determine whether the uddi- tion of glutamine to an elemental diet would aug- ment mucosal adaptation after massive small-bowel resection in a rat model. MATERIALS AND METHODS The animals used in this study were cared for according to the guidelines of the Animal Review Committee at the University of Nebraska Medical Center, Forty 8-week-old male Sprague-Dawley GLUTAMINE AND INTESTINAL ADAPTATION 395 rats weighing ~250 g (Sasco, Omaha, NE, U.S.A.) were acclimatized to the laboratory conditions for 3 ‘days in hanging stainless steel cages. The rats were randomly divided into two groups. One group re- ceived an 80% jejunoileal resection, and the other group were sham operated. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital (5 me/kg); their abdomens were shaved, and the skin was prepped with betadine. A midline abdominal incision was made, the small intestine was located, and the in- tervening vessels were ligated with 5-0 silk. ‘The resection was then performed by removing all bowel between the points 4 cm distal to the ligament of Treitz and 12 em proximal to the ileocecal valve. ‘The remaining jejunum was anastomosed to the midileum using interrupted sutures of 6-0 Dexon (Davis and Geek, Manati, Puerto Rico). The small bowels of sham-operated animals were transected 12 cm proximal to the ileocecal valve and reanasto- mosed. All rats were given access to drinking water containing 5% glucose and 0.0225% tetracycline for 24h Each group of rals was then further divided into two dietary groups, one supplemented with t-glu- tamine (Sigma, St. Louis, MO, U.S.A.), and the other supplemented with glucose. These substances Were mixed in # non-glutamine-containin acid-based pediatric elemental diet (Neocate One +; SHS Inc., Gaithersburg, MD, U.S.A.) Both glucose and glutamine were mixed to obtain final concentration of 2% Analysis Resected and sham animals were killed 15 days postsurgery. As Hanson et al. have noted, adapta tion is nearly complete by that time in the rat (9). ‘The small intestine from the pylorus to the ileocecal valve was carefully removed, stripped of its mesen: tery, and divided at the anastomosis. The bowel was rinsed with cold isotonic saline, and the ends were trimmed to remove any damaged tissues. Bowel segment lengths were determined by laying the segments straight on a wet glass plate and mea- suring with a ruler. The mucosa was scraped, weighed, and subsequently homogenized in deion- ized Water. Mucosal protein was measured by the method of Lowry et al. (10). Deoxyribonucleic acid (DNA) was extracted and measured according to Burton, a modified by Giles (11,12), Disaechar dase activity was measured by the method of Dahl- vist (13) Al results are expressed as the mean * standard error of mean for exch group of animals. Significant differences among means were analyzed using anal- ysis of variance and Duncan's multiple range test (14), Differences were considered statistically siz- nificant at p < 0.08. RESULTS Mean body weights from the start of test dict 10 the 15th postoperative day increased by 44 g in the resected group receiving glutamine supplement tion and 51 g for the resecied group receiving glu cose (p > 0.05). For the sham-operated rats, body ‘weight increments were 80.75 and 80.5 g for the glutamine- and the glucose-supplemented groups, respectively (p > 0.05) (Fig. 1). The difference in incremental weight gain between the glucose- and glutamine-supplemented animals did not reach sta tistical significance on any of the postoperative days. Mucosal weight, protein, DNA content, and sucruse activities showed no significant differences, between the two dietary groups (Tables t and 2). As expected, the resected group showed significantly higher mucosal weight, protein, DNA content, and suerase activities in both duodenum and ileum. DISCUSSION Short bowel syndrome is a condition that results from resection of a large portion of the small bowel (15). In humans, nutrition is maintained parenteral ly during the carly postoperative period. However, long-term parenteral nutrition may eventually be unnecessary for survival because of a process known as intestinal adaptation (16), This process highly dependent upon enteral nutrition (17-21) Several investigators have been interested in iden- Uilying the different nutrients that are most capable of enhancing intestinal adaptation (22-27) Recently there has been an increasing interest in the use of glutamine for several gastrointestinal dis- orders. Glutamine is a neutral amino acid used ex- tensively by the gut, preferentially over glucose. Although it is « nonessential amino acid, it acts asa principal fuel and an important respiratory sub- strate for rapidly dividing cells, especially entero- cytes (5), The skeletal muscles are the major tissues, J Pein Gateautvsl Nar Vol 21, Na 4 BS 396 ‘woight in me o 1 2 5 7 8 1 48 days after surgory involved in glutamine production (28). During per ‘ods of operative stress, the release of from the muscle is accelerated. This acceleration, however, is ussociated with a decrease in circulat- ing concentration of glutamine, suggesting an in- creased cellular uptake. Studies have shown that after surgery, even a standard laparotomy, glu- tamine consumption by the intestinal tract is in- creased by 75% (29). In 1987, Hwang et al. demonstrated that glu- tamine supplementation of total parenteral nutrition solutions prevented mucosal atrophy after partial small-bowel resection in rats (30). Grant also showed that glutamine supplementation of total parenteral nutrition solution promotes intestinal TABLE 1, The effect af glutamine on mucosal weight protein, DNA, and sucrase activity after 806 Jejunoileal resection 5. MICHAIL 4 AL oe reste ete FIG. 1. This figuee represents the increase in body weight fol lowing surgery in relation to dict mucosal height and gut nitrogen content (31). Klim- berg et al, examined glutamine metabolism in the shortened bowel and showed an increase in gut glu- ‘amine utilization associated with an increase in gut cellularity and glutaminase content (7). Glutamine hhas several beneficial effects in experimentally in- duced enterocolitis. These effects include signiti- cantly improved nutritional status, decreased intes- tinal injury, decreased bacterial translocation, re~ duced endotoxemia, and improved survival in this lethal model of enterocolitis (32), ‘The importance of glutamine as a metabolic sub- strate for the small intestine makes it a potential candidate as a facilitator for intestinal adaptation following massive small-bowel resection, Previous TABLE 2, The effects of glutamine on mucosal weight, protein, DNA, and sucrase activity in shani-operated rats Vorabies ‘Guanine ———

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