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Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis

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Abstract

The pathogenesis of necrotizing enterocolitis (NEC) presumptively is due to an inappropriate intestinal epithelial immunologic response of immature gut to luminal stimuli. Glutamine is essential for intestinal crypt cell proliferation and enhances the cellular response to growth factors. We aimed to test the hypothesis that the supplementation of enteral feedings with glutamine may stimulate an immature intestine and decrease the intestinal inflammatory change in NEC. Immediately after birth, the neonatal rats were weighed and randomized into one of four treatment groups. Group 1 consisted of rats whom were breast-fed. Group 2 (NEC group) consisted of neonates whom were fed with a special rodent formula. Rats in groups 3 and 4 were fed in a similar fashion to those in group 2, and glutamine 0.3 mg/kg per day and dexamethasone 0.5 mg/kg per day were added to their formula, respectively. The neonatal rats were weighed and killed on day 4: the last 4 cm of terminal ileum was harvested for morphological studies and detection of nitrite and nitrate levels in tissue. The animals in the NEC group showed various degrees of inflammatory changes similar to clinical NEC. The inflammatory changes of the intestine appeared to be attenuated in both glutamine- and steroid-treated animals compared to those in the NEC group. Only steroid treatment decreased the tissue levels of these nitrogen oxides that were increased in rats in the NEC group. We herein provide evidence that maturational agents such as glutamine and dexametasone can attenuate the local intestinal inflammatory damage in experimental NEC. These findings support the hypothesis that the gut immaturity in premature infants represents a risk factor for NEC.

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References

  1. Barlow B, Santulli TV, Heird WC, Pitt J, Blanc WA, Schullinger JN (1974) An experimental study of acute neonatal enterocolitis-The important of breast milk. J Pediatr Surg 9:587

    PubMed  Google Scholar 

  2. Baskerville A, Hambleton B, Benbough J (1980) Pathological features of glutaminase toxicity. Br J Exp Pathol 61:132–138

    CAS  PubMed  Google Scholar 

  3. Bauer CR, Morrison JC, Poole K, Korones SB, Boehm JJ, Rigatto H, Zachman RD (1984) A decreased incidence of necrotising enterocolitis after prenatal glucocorticoid therapy. Pediatrics 73:682

    CAS  PubMed  Google Scholar 

  4. Becker RM, Wu G, Galanko JA, Chen W, Maynor AR, Bose CL, Rhoads JM (2000) Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 137:785–793

    Article  CAS  PubMed  Google Scholar 

  5. Bellows CF, Jaffe BM (1999) Glutamine is essential for nitric oxide synthesis by murine macrophages. J Surg Res 86:213–219

    Article  CAS  PubMed  Google Scholar 

  6. Ford H, Watkins S, Reblock K, Rowe M (1997) The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg 32:275–282

    CAS  PubMed  Google Scholar 

  7. Goo LL, Ford HR. Watkins SC, Healey PJ, Albanese CT, Donhalek A, Simmons RL, Rowe MI (1994) Quantitative and morphologic analysis of bacterial translocation in neonates. Arch Surg 129:1184–1190

    PubMed  Google Scholar 

  8. Halac E, Halac J, Begue EF, Casanas JM, Indiveri DR, Petit JF, Figueroa MJ, Olmas JM, Rodriguez LA, Obregon RJ (1990) Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. J Pediatr 117:132–138

    PubMed  Google Scholar 

  9. Israel EJ, Schiffrin EJ, Carter EA, Frieberg E, Walker A (1991) Cortisone strengthens the intestinal mucosal barrier in a rodent necrotizing enterocolitis model. Adv Exp Med Biol 310:375–380

    PubMed  Google Scholar 

  10. Le Bacquer O, Nazih H, Blottiere H, Meynial-Denis B, Laboisse C, Darmaun D (2001) Effects of glutamine deprivation on protein synthesis in a model of human enterocytes in culture. Am J Physiol Gastrointest Liver Physiol 281:G1340–1347

    PubMed  Google Scholar 

  11. Lemons JA, Adcock EWI, Jones MD, Naughton MA, Meschia G, Battaglia FC (1976) Umbilical uptake of amino acids in the unstressed fetal lamb. J Clin Invest 58:1428–1434

    PubMed  Google Scholar 

  12. Meininger CJ, Wu G (1997) L-Glutamine inhibits nitric oxide synthesis in bovine venular endothelial cells. J Pharmacol Exp Ther 281:448–453

    PubMed  Google Scholar 

  13. Moshage H, Kok B, Huizenga JR, Jansen PLM (1995) Nitrite and nitrate determinations in plasma: A critical evaluation. Clin Chem 41:892–896

    CAS  PubMed  Google Scholar 

  14. Muguruma K, Gray PW, Tjoelker LW, Johnston JM (1997) The central role of PAF in necrotizing enterocolitis development. Adv Exp Med Biol 407:379–382

    PubMed  Google Scholar 

  15. Nadler EP, Dickinson E, Knisely A, Zhang R, Boyle P, Beer-Stolz D, Watkins SC, Ford HR (2000) Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res 92:71–77

    Article  CAS  PubMed  Google Scholar 

  16. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA (2000) Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci USA 97:6043–6048

    Article  PubMed  Google Scholar 

  17. Neu J, Roig JC, Meetze WH, Veerman M, Carter C, Millsaps M, Bowling D, Dallas MJ, Sleasman J, Knight T, Auestad N (1997) Enteral glutamine supplementation for very low birth weight infants decreases morbidity. J Pediatr 131:691–699

    CAS  PubMed  Google Scholar 

  18. Papaconstantinou HT, Hwang KO, Rajaraman S, Hellmich MR, Townsend CM, Ko TC (1998) G Glutamine deprivation induces apoptosis in intestinal epithelial cells. Surgery 124:152–160

    Article  PubMed  Google Scholar 

  19. Rhoads JM, Argenzio RA, Chen W, Rippe RA, Westwick JK, Cox AD et al (1997) L-Glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases. AM J Physiol 35:G943–953

    Google Scholar 

  20. Sarantos P, Abouhamze Z, Copeland EM, Souba WW (1994) Glucocorticoids regulate glutaminase gene expression in human intestinal epithelial cells. J Surg Res 57:227–231

    Article  PubMed  Google Scholar 

  21. Sauba WW, Smith RJ, Wilmore DW (1985) Glutamine metabolism by the intestinal tract. JPEN J Parenter Enteral Nutr 9:608–617

    PubMed  Google Scholar 

  22. Tepperman BL, Brown JF, Whittle BJ (1993) Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol 265:G214–218

    CAS  PubMed  Google Scholar 

  23. Veereman-Wauters G, Deutz NE, Roman C, Meyers R, Rudolph CD (1992) Amino acid gradients across the intestinal circulation in fetal lambs. J Dev Physiol 17:143–146

    PubMed  Google Scholar 

  24. Whittle BJR (1995) Nitric oxide in physiology and pathology. Histochem J 27:727–737

    CAS  PubMed  Google Scholar 

  25. Wood BR, Huddleston KC, Frazier T (1991) Glutamine levels in amniotic fluid, breast milk, and premature infant formula: non-essential amino acid or essential nutrient (abstract). J Pediatr Res 29:306A

    Google Scholar 

  26. Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424

    PubMed  Google Scholar 

  27. Wu G, Bazer FW, Tuo W (1995) Developmental changes of free amino acid concentrations in fetal fluids of pigs. J Nutr 125:2859–2868

    PubMed  Google Scholar 

  28. Wu G, Knabe DA, Bazer FW (1999) Amino acid composition of fetal pig. J Nutr 129:1031–1038

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Surgery of Meram Medical Faculty, Selçuk University, 42080, Konya, Turkey

    Alaeddin Dilsiz & İlhan Çiftçi

  2. Department of Histology of Meram Medical Faculty, Selçuk University, Konya, Turkey

    T. Murad Aktan

  3. Department of Biochemistry of Meram Medical Faculty, Selçuk University, Konya, Turkey

    Mehmet Gürbilek & Emrah Karagözoğlu

Authors
  1. Alaeddin Dilsiz
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  2. İlhan Çiftçi
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  3. T. Murad Aktan
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  4. Mehmet Gürbilek
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  5. Emrah Karagözoğlu
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Correspondence to Alaeddin Dilsiz.

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Dilsiz, A., Çiftçi, İ., Aktan, T.M. et al. Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis. Ped Surgery Int 19, 578–582 (2003). https://doi.org/10.1007/s00383-003-0980-y

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