This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Fox, A. D. Articles by Rombeau, J. L. Search for Related Content PubMed PubMed Citation Articles by Fox, A. D. Articles by Rombeau, J. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB METHOTREXATE Social Bookmarking                         What's this?

Effect of a Glutamine-Supplemented Enteral Diet on Methotrexate-Induced Enterocolitis

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

Scott A. Kripke, M.D.

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

Juan De Paula, M.D.

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

Jeffery M. Berman, B.A.

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

R. Gregg Settle, PH.D.

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

John L. Rombeau, M.D.

Departments of Surgery and Otorhinolaryngology, University of Pennsylvania and the Philadelphia Veterans Medical Center, Philadelphia, Pennsylvania

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut' and may facilitate intestinal recovery after injury.² This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon.

In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality.

In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia.

These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis. (Journal of Parenteral and Enteral Nutrition 12:325-331, 1988)

Journal of Parenteral and Enteral Nutrition, Vol. 12, No. 4, 325-331 (1988)
DOI: 10.1177/0148607188012004325


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Tian, L. Hao, P. Chandra, D. P. Jones, I. R. Willams, A. T. Gewirtz, and T. R. Ziegler Dietary glutamine and oral antibiotics each improve indexes of gut barrier function in rat short bowel syndrome Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G348 - G355. [Abstract] [Full Text] [PDF]

				S. D. Larson, J. Li, D. H. Chung, and B. M. Evers Molecular mechanisms contributing to glutamine-mediated intestinal cell survival Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1262 - G1271. [Abstract] [Full Text] [PDF]

				M. Vicario, C. Amat, M. Rivero, M. Moreto, and C. Pelegri Dietary Glutamine Affects Mucosal Functions in Rats with Mild DSS-Induced Colitis J. Nutr., August 1, 2007; 137(8): 1931 - 1937. [Abstract] [Full Text] [PDF]

				A. van den Berg, W. P. F. Fetter, E. A. M. Westerbeek, I. M. van der Vegt, H. R. A. van der Molen, and R. M. van Elburg The Effect of Glutamine-Enriched Enteral Nutrition on Intestinal Permeability in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial JPEN J Parenter Enteral Nutr, September 1, 2006; 30(5): 408 - 414. [Abstract] [Full Text] [PDF]

				A. van den Berg, R. M van Elburg, E. A. Westerbeek, J. W. Twisk, and W. P. Fetter Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1397 - 1404. [Abstract] [Full Text] [PDF]

				N. Li, K. Liboni, M. Z. Fang, D. Samuelson, P. Lewis, R. Patel, and J. Neu Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats Am J Physiol Gastrointest Liver Physiol, June 1, 2004; 286(6): G914 - G921. [Abstract] [Full Text] [PDF]

				S. W. Dixon Integrative Tumor Board: Colon Cancer with Liver Metastases Integr Cancer Ther, June 1, 2003; 2(2): 173 - 180. [PDF]

				M. Muscaritoli, G. Grieco, S. Capria, A. Paola Iori, and F. Rossi Fanelli Nutritional and metabolic support in patients undergoing bone marrow transplantation Am. J. Clinical Nutrition, February 1, 2002; 75(2): 183 - 190. [Abstract] [Full Text] [PDF]

				B Daniele, F Perrone, C Gallo, S Pignata, S De Martino, R De Vivo, E Barletta, R Tambaro, R Abbiati, and L D'Agostino Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial Gut, January 1, 2001; 48(1): 28 - 33. [Abstract] [Full Text] [PDF]

				T. M. Coghlin Dickson, R. M. Wong, R. S. Negrin, J. A. Shizuru, L. J. Johnston, W. W. Hu, K. G. Blume, and K. E. Stockerl-Goldstein Effect of Oral Glutamine Supplementation During Bone Marrow Transplantation JPEN J Parenter Enteral Nutr, March 1, 2000; 24(2): 61 - 66. [Abstract] [PDF]

				D. Savarese, A. Al-Zoubi, and J. Boucher Glutamine for Irinotecan Diarrhea J. Clin. Oncol., January 14, 2000; 18(2): 450 - 450. [Full Text]

				S. Aosasa, H. Mochizuki, T. Yamamoto, S. Ono, and T. Ichikura A Clinical Study of the Effectiveness of Oral Glutamine Supplementation During Total Parenteral Nutrition: Influence on Mesenteric Mononuclear Cells JPEN J Parenter Enteral Nutr, September 1, 1999; 23(5_suppl): S41 - S44. [Abstract] [PDF]

				J. Neu, V. DeMarco, and M. Weiss Glutamine Supplementation in Low-Birth-Weight Infants: Mechanisms of Action JPEN J Parenter Enteral Nutr, September 1, 1999; 23(5_suppl): S49 - S51. [Abstract] [PDF]

				M. D. Weiss, V. DeMarco, D. M. Strauss, D. A. Samuelson, M. E. Lane, and J. Neu Glutamine Synthetase: A Key Enzyme for Intestinal Epithelial Differentiation? JPEN J Parenter Enteral Nutr, May 1, 1999; 23(3): 140 - 146. [Abstract] [PDF]

				J. S. Marchini, P. Nguyen, J.-Y. Deschamps, P. Maugere, M. Krempf, and D. Darmaun Effect of intravenous glutamine on duodenal mucosa protein synthesis in healthy growing dogs Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E747 - E753. [Abstract] [Full Text] [PDF]

				C. Ford and J. B. Pietsch Home Enteral Tube Feeding in Children After Chemotherapy or Bone Marrow Transplantation Nutr Clin Pract, February 1, 1999; 14(1): 19 - 22. [Abstract] [PDF]

				A. Chow and R. Zhang Glutamine Reduces Heat Shock-Induced Cell Death in Rat Intestinal Epithelial Cells J. Nutr., August 1, 1998; 128(8): 1296 - 1301. [Abstract] [Full Text]

				D. A. De-Souza and L. J. Greene Pharmacological Nutrition After Burn Injury J. Nutr., May 1, 1998; 128(5): 797 - 803. [Abstract] [Full Text]

				C K Ameho, A A Adjei, E K Harrison, K Takeshita, T Morioka, Y Arakaki, E Ito, I Suzuki, A D Kulkarni, A Kawajiri, et al. Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha  production in trinitrobenzene sulphonic acid induced colitis Gut, October 1, 1997; 41(4): 487 - 493. [Abstract] [Full Text] [PDF]

				P. Panigrahi, I. H. Gewolb, P. Bamford, and K. Horvath Role of Glutamine in Bacterial Transcytosis and Epithelial Cell Injury JPEN J Parenter Enteral Nutr, March 1, 1997; 21(2): 75 - 80. [Abstract] [PDF]

				K. Horvath, M. Jami, I.D. Hill, J.C. Papadimitriou, L. S. Magder, and S. Chanasongcram Isocaloric Glutamine-Free Diet and the Morphology and Function of Rat Small Intestine JPEN J Parenter Enteral Nutr, March 1, 1996; 20(2): 128 - 134. [Abstract] [PDF]

				J. M. Lacey, J. B. Crouch, K. Benfell, S. A. Ringer, C. K. Wilmore, D. Maguire, and D. W. Wilmore The Effects of Glutamine-Supplemented Parenteral Nutrition in Premature Infants JPEN J Parenter Enteral Nutr, January 1, 1996; 20(1): 74 - 80. [Abstract] [PDF]

				R. Gennari, J. W. Alexander, and T. Eaves-Pyles Effect of Different Combinations of Dietary Additives on Bacterial Translocation and Survival in Gut-Derived Sepsis JPEN J Parenter Enteral Nutr, July 1, 1995; 19(4): 319 - 325. [Abstract] [PDF]

				J.C. Roig, V. B. Shenoy, R. Chakrabarti, J. Y.N. Lau, and J. Neu Localization of Rat Small Intestine Glutamine Synthetase Using Immunofluorescence and In Situ Hybridization JPEN J Parenter Enteral Nutr, May 1, 1995; 19(3): 179 - 181. [Abstract] [PDF]

				D. Royall, G. R. Greenberg, J. P. Allard, J. P. Baker, and K. N. Jeejeebhoy Total Enteral Nutrition Support Improves Body Composition of Patients With Active Crohn's Disease JPEN J Parenter Enteral Nutr, March 1, 1995; 19(2): 95 - 99. [Abstract] [PDF]

				L. Gianotti, J. W. Alexander, R. Gennari, T. Pyles, and G. F. Babcock Oral Glutamine Decreases Bacterial Translocation and Improves Survival in Experimental Gut-Origin Sepsis JPEN J Parenter Enteral Nutr, January 1, 1995; 19(1): 69 - 74. [Abstract] [PDF]

				M. J. Fahr, J. Kornbluth, S. Blossom, R. Schaeffer, and V. S. Kumberg Glutamine Enhances Immunoregulation of Tumor Growth JPEN J Parenter Enteral Nutr, November 1, 1994; 18(6): 471 - 476. [Abstract] [PDF]

				R. G. Barton Invited Review: Nutrition Support in Critical Illness Nutr Clin Pract, August 1, 1994; 9(4): 127 - 139. [Abstract] [PDF]

				D. G. Burrin, R. J. Shulman, C. Langston, and M. C. Storm Supplemental Alanylglutamine, Organ Growth, and Nitrogen Metabolism in Neonatal Pigs Fed by Total Parenteral Nutrition JPEN J Parenter Enteral Nutr, July 1, 1994; 18(4): 313 - 319. [Abstract] [PDF]

				R. Babst, H. Horig, P. Stehle, O. Brand, L. Filgueira, W. Marti, M. Fischer, M. Oberholzer, F. Gudat, P. Furst, et al. Glutamine Peptide-Supplemented Long-Term Total Parenteral Nutrition: Effects on Intracellular and Extracellular Amino Acid Patterns, Nitrogen Economy, and Tissue Morphology in Growing Rats JPEN J Parenter Enteral Nutr, November 1, 1993; 17(6): 566 - 574. [Abstract] [PDF]

				G. Spaeth, T. Gottwald, W. Haas, and M. Holmer Glutamine Peptide Does Not Improve Gut Barrier Function and Mucosal Immunity in Total Parenteral Nutrition JPEN J Parenter Enteral Nutr, July 1, 1993; 17(4): 317 - 323. [Abstract] [PDF]

				C. Platell, R. Mccauley, R. Mcculloch, and J. Hall The Influence of Parenteral Glutamine and Branched-Chain Amino Acids on Total Parenteral Nutrition--Induced Atrophy of the Gut JPEN J Parenter Enteral Nutr, July 1, 1993; 17(4): 348 - 354. [Abstract] [PDF]

				H. Tamada, R. Nezu, Y. Matsuo, I. Imamura, Y. Takagi, and A. Okada Alanyl Glutamine-Enriched Total Parenteral Nutrition Restores Intestinal Adaptation After Either Proximal or Distal Massive Resection in Rats JPEN J Parenter Enteral Nutr, May 1, 1993; 17(3): 236 - 242. [Abstract] [PDF]

				S. Jima, T. Tsujinaka, Y. Kido, Y. Hayashida, H. Ishida, T. Homma, H. Yokoyama, and T. Mori Intravenous Administration of Nucleosides and a Nucleotide Mixture Diminishes Intestinal Mucosal Atrophy Induced by Total Parenteral Nutrition JPEN J Parenter Enteral Nutr, May 1, 1993; 17(3): 265 - 270. [Abstract] [PDF]

				K. Gardiner and A. Barbul Review: Intestinal Amino Acid Absorption During Sepsis JPEN J Parenter Enteral Nutr, May 1, 1993; 17(3): 277 - 283. [Abstract] [PDF]

				Y. Inoue, J. P. Grant, and P. J. Snyder Effect of Glutamine-Supplemented Total Parenteral Nutrition on Recovery of the Small Intestine After Starvation Atrophy JPEN J Parenter Enteral Nutr, March 1, 1993; 17(2): 165 - 170. [Abstract] [PDF]

				Y. Inoue, J. P. Grant, and P. J. Snyder Effect of Glutamine-Supplemented Intravenous Nutrition on Survival After Escherichia coli-Induced Peritonitis JPEN J Parenter Enteral Nutr, January 1, 1993; 17(1): 41 - 46. [Abstract] [PDF]

				F. Ziegler, C. Coudray-Lucas, A. Jardel, E. Lasnier, J. Le Boucher, O. G. Ekindjian, and L. Cynober Ornithine {alpha}-Ketoglutarate and Glutamine Supplementation During Refeeding of Food-Deprived Rats JPEN J Parenter Enteral Nutr, November 1, 1992; 16(6): 505 - 510. [Abstract] [PDF]

				T. Jones, R. Tao, G. L. Blackburn, W. S. Swails, and S. J. Bell Letters Nutr Clin Pract, August 1, 1992; 7(4): 197 - 198. [PDF]

				T. R. Ziegler, L. S. Young, K. Benfell, M. Scheltinga, K. Hortos, R. Bye, F. D. Morrow, D. O. Jacobs, R. J. Smith, J. H. Antin, et al. Clinical and Metabolic Efficacy of Glutamine-supplemented Parenteral Nutrition after Bone Marrow Transplantation: A Randomized, Double-Blind, Controlled Study Ann Intern Med, May 15, 1992; 116(10): 821 - 828. [Abstract] [PDF]

				W. S. Swails, S. J. Bell, B. C. Borlase, R. A. Forse, and G. L. Blackburn Glutamine Content of Whole Proteins: Implications for Enteral Formulas Nutr Clin Pract, April 1, 1992; 7(2): 77 - 80. [Abstract] [PDF]

				H. Tamada, R. Nezu, I. Imamura, Y. Matsuo, Y. Takagi, S. Kamata, and A. Okada The Dipeptide Alanyl-Glutamine Prevents Intestinal Mucosal Atrophy in Parenterally Fed Rats JPEN J Parenter Enteral Nutr, March 1, 1992; 16(2): 110 - 116. [Abstract] [PDF]

				W. Scheppach, P. Bartram, A. Richter, F. Richter, H. Liepold, G. Dusel, G. Hofstetter, J. Ruthlein, and H. Kasper Effect of Short-Chain Fatty Acids on the Human Colonic Mucosa in Vitro JPEN J Parenter Enteral Nutr, January 1, 1992; 16(1): 43 - 48. [Abstract] [PDF]

				Jian Shou, M. D. Lieberman, K. Hofmann, P. Leon, H. P. Redmond, H. Davies, and J. M. Daly Dietary Manipulation of Methotrexate-Induced Enterocolitis JPEN J Parenter Enteral Nutr, May 1, 1991; 15(3): 307 - 312. [Abstract] [PDF]

				J. M. Talbot Guidelines for the Scientific Review of Enteral Food Products for Special Medical Purposes JPEN J Parenter Enteral Nutr, May 1, 1991; 15(3_suppl): i - E-2. [PDF]

				G. P. Zaloga Invited Review: Physiologic Effects of Peptide-Based Enteral Formulas Nutr Clin Pract, December 1, 1990; 5(6): 231 - 237. [PDF]

				D. A. Plumley, T. R. Austgen, R. M. Salloum, and W. W. Souba Role of the Lungs in Maintaining Amino Acid Homeostasis JPEN J Parenter Enteral Nutr, November 1, 1990; 14(6): 569 - 573. [Abstract] [PDF]

				A. Abad-Lacruz, F. Gonzalez-Huix, M. Esteve, F. Fernandez-Banares, E. Cabre, J. Boix, D. Acero, P. Humbert, and M. A. Gassull Liver Function Tests Abnormalities in Patients with Inflammatory Bowel Disease Receiving Artificial Nutrition: A Prospective Randomized Study of Total Enteral Nutrition vs Total Parenteral Nutrition JPEN J Parenter Enteral Nutr, November 1, 1990; 14(6): 618 - 621. [Abstract] [PDF]

				J. W. Alexander Nutrition and Translocation JPEN J Parenter Enteral Nutr, September 1, 1990; 14(5_suppl): 170S - 174S. [Abstract] [PDF]

				W. W. Souba, K. Herskowitz, T. R. Austgen, M. K. Chen, and R. M. Salloum Glutamine Nutrition: Theoretical Considerations and Therapeutic Impact JPEN J Parenter Enteral Nutr, September 1, 1990; 14(5_suppl): 237S - 243S. [PDF]

				A. E. Barber, W. G. Jones II, J. P. Minei, T. J. Fahey III, L. L. Moldawer, J. L. Rayburn, E. Fischer, C. V. Keogh, G. T. Shires, and S. F. Lowry Glutamine or Fiber Supplementation of a Defined Formula Diet: Impact on Bacterial Translocation, Tissue Composition, and Response to Endotoxin JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4): 335 - 343. [Abstract] [PDF]

				R. J. Smith Glutamine Metabolism and Its Physiologic Importance JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 40S - 44S. [Abstract] [PDF]

				W. W. Souba, K. Herskowitz, R. M. Salloum, M. K. Chen, and T. R. Austgen Gut Glutamine Metabolism JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 45S - 50S. [PDF]

				R. J. Smith and D. W. Wilmore Glutamine Nutrition and Requirements JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 94S - 99S. [Abstract] [PDF]

				J. L. Rombeau A Review of the Effects of Glutamine-Enriched Diets on Experimentally Induced Enterocolitis JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 100S - 105S. [PDF]

				T. R. Ziegler, K. Benfell, R. J. Smith, L. S. Young, E. Brown, E. Ferrari-Baliviera, D. K. Lowe, and D. W. Wilmore Safety and Metabolic Effects of L-Glutamine Administration in Humans JPEN J Parenter Enteral Nutr, July 1, 1990; 14(4_suppl): 137S - 146S. [Abstract] [PDF]

				D. W. Wilmore Rhoads lecture. The Practice of Clinical Nutrition: How To Prepare for the Future JPEN J Parenter Enteral Nutr, July 1, 1989; 13(4): 337 - 343. [PDF]