Skip to main content

Advertisement

SpringerLink
Log in

Dietary Glutamine Supplementation Prevents Mucosal Injury and Modulates Intestinal Epithelial Restitution Following Ischemia-Reperfusion Injury in the Rat

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The aim of the present study was to evaluate the preventive effect of a 2-day oral glutamine supplementation against intestinal ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into four experimental groups: sham rats underwent laparotomy, sham-GLU rats underwent laparotomy and were treaded with enteral glutamine (GLU) given in drinking water (2%) 48 hr before and following operation, IR rats underwent occlusion of both the superior mesenteric artery and the portal vein for 30 min followed by 24 hr of reperfusion, and IR-GLU rats were treated with enteral glutamine 48 hr before and following IR. Intestinal mucosal damage (Park’s injury score), mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 hr following IR. Sham-GLU rats demonstrated a lower rate of cell apoptosis in jejunum and ileum compared to sham animals. IR-GLU animals demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA, villous height and crypt depth, and enterocyte proliferation index in ileum and a lower injury score grade in jejunum compared to IR-nontreated rats. In conclusion, pretreatment with oral glutamine prevents mucosal injury and improves intestinal recovery following IR injury in the rat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Deitch EA (1992) Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg 216:117–134

    Article  PubMed  CAS  Google Scholar 

  2. Granger DN, Hollwarth ME, Park DA (1986) Ishemia reperfusion injury: role of oxygen-derived free radicals. Acta Physiol Scand Suppl 548:47–56

    PubMed  CAS  Google Scholar 

  3. Carden DL, Granger DN (2000) Pathophysiology of ischaemia-reperfusion injury. J Pathol 190:255–266

    Article  PubMed  CAS  Google Scholar 

  4. Mangino MJ, Mangino JE, Murphy MK, Anderson CB (1996) Arachidonic acid metabolism in intestinal hypothermic preservation injury. Cryobiology 33:404–412

    Article  PubMed  CAS  Google Scholar 

  5. Kurose I, Argenbright LW, Wolf R, Lianxi L, Granger DN (1997) Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators. Am J Physiol 272: H2976–H2982

    PubMed  CAS  Google Scholar 

  6. Yamamoto S, Tanabe M, Wakabayashi G, Shimazu M, Matsumoto K, Kitajima M (2001) The role of tumor necrosis factor-alpha and interleukin-1beta in ischemia-reperfusion injury of the rat small intestine. J Surg Res 99:134–141

    Article  PubMed  CAS  Google Scholar 

  7. Schoenberg MH, Poch B, Younes M, Schwarz A, Baczako K, Lundberg C, Haglund U, Beger HG (1991) Involvement of neutrophils in postischaemic damage to the small intestine. Gut 32:905–1112

    PubMed  CAS  Google Scholar 

  8. Sun Z, Wang X, Deng X, Boriesson A, Wallen R, Hallberg E, Andersson R (2000) Phagocytic and intestinal endothelial and epithelial barrier function during the early stage of small intestinal ischemia and reperfusion injury. Shock 13:209-216

    PubMed  Google Scholar 

  9. Noda T, Iwakiri R, Fujimoto K, Matsuo S, Aw TY (1998) Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa. Am J Physiol 274:G270

    PubMed  CAS  Google Scholar 

  10. Van Der Hulst RR, von Meyenfeldt MF, Soeters PB (1996) Glutamine: an essential amino acid for the gut. Nutrition 12(Suppl 11–12):S78–S81

    Article  PubMed  CAS  Google Scholar 

  11. Windmuelle HG, Spaeth AE (1974) Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 249:5070–5079

    Google Scholar 

  12. Craig M, Coopersmith M, O’Donnell D, Gordon JI (1999) Bcl-2 inhibits ischemia-reperfusion-induced apoptosis in the intestinal epithelium of transgenic mice. Am J Physiol Gastrointest Liver Physiol 276:G677–G686

    Google Scholar 

  13. Chomczynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Bio Techniques 15:532–536

    CAS  Google Scholar 

  14. Park PO, Haglund U, Bulkley GB, Falt K (1990) The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion. Surgery 107:574–580

    PubMed  CAS  Google Scholar 

  15. Noda T, Ivakiri R, Fujimoto K, Matsuo S, Aw TY (1998) Programmed cell death induced by IR in rat intestinal mucosa. Am J Physiol 274:270–276

    Google Scholar 

  16. Buttke JM, Sandrtrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    Article  PubMed  CAS  Google Scholar 

  17. Melis GC, ter Wengel N, Belens PG, van Leeuwen PA (2004) Glutamine: recent developments in research on the clinical significance of glutamine. Curr Opin Clin Nutr Metab Care 7:59–70

    Article  PubMed  CAS  Google Scholar 

  18. Chapman MA, Grahn MF, Giamundo P, O’Connell PR, Onwu D, Hutton M, Maudsley J, Norton B, Rogers J, Williams NS (1993) New technique to measure mucosal metabolism and its use to map substrate utilization in the healthy human large bowel. Br J Surg 80:445–449

    Article  PubMed  CAS  Google Scholar 

  19. Ikeda S, Zarzaur BL, Johnson CD, Fukatsu K, Kudsk KA (2002) Total parenteral nutrition supplementation with glutamine improves survival after gut ischemia/reperfusion. J Parent Enteral Nutr 26:169–173

    CAS  Google Scholar 

  20. Fukatsu K, Ueno C, Hashiguchi Y, Hara E, Kinoshita M, Mochizuki H, Hiraide H (2003) Glutamine infusion during ischemia detrimental in a murine gut ischemia/reperfusion model. J Parent Enteral Nutr 27:187–192

    CAS  Google Scholar 

  21. Wu GH, Wang H, Zhang YW, Wu ZH, Wu ZG (2004) Glutamine supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats. World J Gastroenterol 10: 2592–2594

    PubMed  CAS  Google Scholar 

  22. Wasa M, Soh H, Shimizu Y, Fukuzawa M (2005) Glutamine stimulates amino acid transport during ischemia-reperfusion in human intestinal epithelial cells. J Surg Res 123:75–81

    Article  PubMed  CAS  Google Scholar 

  23. Sato N, Moore FA, Smith MA, Zou L, Moore-Olufemi S, Kozar RA (2005) Immune-enhancing enteral nutrients differentially modulate the early proinflammatory transcription factors mediating gut ischemia/reperfusion. Trauma 58:455–461

    Article  CAS  Google Scholar 

  24. Higashiguchi T, Hasselgren PO, Wagner K, Fischer JE (1993) Effect of glutamine on protein synthesis in isolated intestinal epithelial cells. J Parent Enteral Nutr 17:307–314

    CAS  Google Scholar 

  25. Sukhotnik I, Helou H, Mogilner J, Lurie M, Bernshteyn A, Coran AG, Shiloni E (2005) Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat. Pediatr Surg Int 21:191–196

    Article  PubMed  Google Scholar 

  26. Wiren M, Magnusson KE, Larsson J (1998) The role of glutamine, serum and energy factors in growth of enterocyte-like cell lines. Int J Biochem Cell Biol 30:1331–1336

    Article  PubMed  CAS  Google Scholar 

  27. Wasa M, Wang HS, Shimisu Y, Okada A (2004) Amino acid transport is down-regulated in ischemic human intestinal epithelial cells. Biochim Biophys Acta 1670:49–55

    PubMed  CAS  Google Scholar 

  28. Kles KA, Turner JR, Tappenden KA (2002) 2001 Harry M. Vars Research Award. Enteral nutrients alter enterocyte function within an in vitro model similar to an acute in vivo rat model during hypoxia. J Parent Enteral Nutr 26:71–76

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb Street, P.O.B. 4940, Haifa, 31048, Israel

    Igor Sukhotnik & Jorge G. Mogilner

  2. Department of Surgery, Carmel Medical Center, The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel

    Kamal Khateeb, Habib Helou & Eitan Shiloni

  3. Department of Pathology, Bnai Zion Medical Center, Haifa, Israel

    Michael Lurie

  4. Section of Pediatric Surgery, C. S. Mott Children’s Hospital and University of Michigan Medical School, Ann Arbor, Michigan, USA

    Arnold G. Coran

Authors
  1. Igor Sukhotnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamal Khateeb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorge G. Mogilner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Habib Helou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Lurie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arnold G. Coran
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eitan Shiloni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Igor Sukhotnik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sukhotnik, I., Khateeb, K., Mogilner, J.G. et al. Dietary Glutamine Supplementation Prevents Mucosal Injury and Modulates Intestinal Epithelial Restitution Following Ischemia-Reperfusion Injury in the Rat. Dig Dis Sci 52, 1497–1504 (2007). https://doi.org/10.1007/s10620-006-9629-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9629-8

Keywords

Search

Navigation