Skip to main content

Advertisement

SpringerLink
Log in

Comparing beneficial effects of inhaled nitric oxide to l-arginine in necrotizing enterocolitis model in neonatal rats

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Objective

Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal condition of neonatal infants. The pathophysiology of NEC remains poorly understood. We tried to evaluate the effectiveness of inhaled NO compared to l-arginine usage in necrotizing enterocolitis model in rats.

Material-methods

46 newborn pups from 4 time-mated Sprague-Dawley pregnant rats were divided equally into 4 groups as follows: NEC (subjected to NEC), NEC + l-arginine, NEC + inhaled NO and control.

Results

SOD, GSH-Px and NOx levels were significantly higher and MDA levels were significantly lower in NEC + inhaled NO group compared to NEC + l-arginine group. There was significantly lower intestinal injury and apoptosis index scoring in NEC + inhaled NO group compared to NEC + l-arginine group.

Conclusion

We think that inhaled NO can be used as a novel therapeutic agent like l-arginine in NEC, like using in pulmonary hypertention in newborns but much more studies are needed.

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

Similar content being viewed by others

References

  1. Jilling T, Lu J, Jackson M, Caplan MS (2004) Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis. Pediatr Res 55:622–629

    Article  PubMed  Google Scholar 

  2. Lin PW, Stoll BJ (2006) Necrotising enterocolitis. Lancet 368:1271–1283

    Article  PubMed  Google Scholar 

  3. Kafetzis DA, Skevaki C, Costalos C (2003) Neonatal necrotizing enterocolitis: an overview. Curr Opin Infect Dis 16:349–355

    Article  PubMed  CAS  Google Scholar 

  4. Hsueh W, Caplan MS, Qu XW, Tan XD, De Plaen IG, Gonzalez-Crussi F (2003) Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr Dev Pathol 6:6–23

    Article  PubMed  Google Scholar 

  5. Di Lorenzo M, Krantis A (2002) Nitric oxide synthase isoenzyme activities in a premature piglet model of necrotizing enterocolitis: effects of nitrergic manipulation. Pediatr Surg Int 18:624–629

    Article  PubMed  Google Scholar 

  6. Stark ME, Szurszewski JH (1992) Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology 103:1928–1949

    PubMed  CAS  Google Scholar 

  7. Boeckxstaens GE, Pelckmans PA, Bult H, De Man JG, Herman AG, van Maercke YM (1991) Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut. Br J Pharmacol 102:434–438

    Article  PubMed  CAS  Google Scholar 

  8. Akisu M, Ozmen D, Baka M, Habif S, Yalaz M, Arslanoglu S et al (2002) Protective effect of dietary supplementation with l-arginine and L-carnitine on hypoxia/reoxygenation-induced necrotizing enterocolitis in young mice. Biol Neonate 81:260–265

    Article  PubMed  CAS  Google Scholar 

  9. Kosonen O, Kankaanranta H, Malo-Ranta U et al (1999) Nitric oxide-releasing compounds inhibit neutrophil adhesion to endothelial cells. Eur J Pharmacol 382:111

    Article  PubMed  CAS  Google Scholar 

  10. Zamora SA, Amin HJ, McMillan DD, Kubes P, Fick GH, Butzner JD, Parsons HG, Scott RB (1997) Plasma l-arginine concentrations in premature infants with necrotizing enterocolitis. J Pediatr 131:226–232

    Article  PubMed  CAS  Google Scholar 

  11. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  12. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  13. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    PubMed  CAS  Google Scholar 

  14. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  15. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71

    Article  PubMed  CAS  Google Scholar 

  16. Zani A, Cordischi L, Cananzi M, De Coppi P, Smith VV, Eaton S, Pierro A (2008) Assessment of a neonatal rat model of necrotizing enterocolitis. Eur J Pediatr Surg 18:423–426

    Article  PubMed  CAS  Google Scholar 

  17. Nadler EP, Dickinson E, Knisely A et al (2000) Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res 92:71–77

    Article  PubMed  CAS  Google Scholar 

  18. Jilling T, Lu J, Jackson M et al (2004) Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis. Pediatr Res 55:622–629

    Article  PubMed  Google Scholar 

  19. Zaky A, Siriussawakul A, Tostenrud RP, Pauldine R, Lang JD Jr (2009) Clinical update on therapeutic use of nitric oxide. Contemp Crit Care 7:1–12

    Google Scholar 

  20. McMahon TJ, Doctor A (2006) Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin. Proc Am Thorac Soc 3:153–160

    Article  PubMed  Google Scholar 

  21. Fox-Robichaud A, Payne D, Hasan SU, Ostrovsky L, Fairhead T, Reinhardt P, Kubes P (1998) Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds. J Clin Invest 101:2497–2505

    Article  PubMed  CAS  Google Scholar 

  22. Adrie C, Bloch KD, Moreno PR, Hurford WE, Guerrero JL, Holt R, Zapol WM, Gold HK, Semigran MJ (1996) Inhaled nitric oxide increases coronary artery patency after thrombolysis. Circulation 94:1919–1926

    Article  PubMed  CAS  Google Scholar 

  23. Fox-Robichaud A, Payne D, Kubes P (1999) Inhaled NO reaches distal vasculatures to inhibit endothelium- but not leukocyte-dependent cell adhesion. Am J Physiol 277:L1224–L1231

    PubMed  CAS  Google Scholar 

  24. Bacha EA, Sellak H, Murakami S, Mazmanian GM, De′ truit H, de Montpreville V, Chapelier AR, Libert JM, Dartevelle PG, Herve′ P (1997) Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung transplantation. Paris-Sud University Lung Transplantation Group. Transplantation 63:1380–1386

    Article  PubMed  CAS  Google Scholar 

  25. Date H, Triantafillou AN, Trulock EP, Pohl MS, Cooper JD, Patterson GA (1996) Inhaled nitric oxide reduces human lung allograft dysfunction. J Thorac Cardiovasc Surg 111:913–919

    Article  PubMed  CAS  Google Scholar 

  26. Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP (2007) Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 117:2583–2591

    Article  PubMed  CAS  Google Scholar 

  27. Siriussawakul A, Zaky A, Lang JD (2010) Role of nitric oxide in hepatic ischemia-reperfusion injury. World J Gastroenterol 16(48):6079–6086

    Article  PubMed  CAS  Google Scholar 

  28. Köken T, Inal M (1999) The effect of nitric oxide on ischemia-reperfusion injury in rat liver. Clin Chimi Acta 288:55–62

    Article  Google Scholar 

  29. Cannon RO 3rd, Schechter AN, Panza JA, Ognibene FP, Pease-Fye ME, Waclawiw MA, Shelhamer JH, Gladwin MT (2001) Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 108:279–287

    PubMed  CAS  Google Scholar 

  30. Ambalavanan N, El-Ferzli GT, Roane C, Johnson R, Carlo WA (2009) Nitric oxide administration using an oxygen hood: a pilot trial. PLoS One 4:e4312

    Article  PubMed  Google Scholar 

  31. Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115:1232–1240

    PubMed  CAS  Google Scholar 

  32. Estevez AG, Radi R, Barbeito L, Shin JT, Thompson JA, Beckman JS (1995) Peroxynitrite-induced cytotoxicity in PC12 cells: evidence for an apoptotic mechanism differentially modulated by neurotrophic factors. J Neurochem 65(4):1543–1550

    Article  PubMed  CAS  Google Scholar 

  33. Lin KT, Xue JY, Nomen M, Spur B, Wong PY (1995) Peroxynitrite-induced apoptosis in HL-60 cells. J Biol Chem 270(28):16487–16490

    Article  PubMed  CAS  Google Scholar 

  34. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T (1978) Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187:1–7

    Article  PubMed  CAS  Google Scholar 

  35. Amin H, Soraisham AS, Sauve R (2006) Does l-arginine supplementation used in the prevention of NEC in < or = 1250gm birth weight infants adversely impact neurodevelopment? E-PAS 59(2862):228

    Google Scholar 

  36. Amin HJ, Zamora SA, McMillan DD, Fick GH, Butzner JD, Parsons HG, Scott RB (2002) Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr 140:425

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors do not have any conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Pediatrics, GATA Medical Faculty, Ankara, Turkey

    Ferhat Çekmez, Kürşat Fidancı, Abdülbaki Karaoğlu, Oğuzhan Babacan, Fuat Emre Canpolat, Merih Çetinkaya & Turan Tunc

  2. Anesthesiology Service, Gulhane Military Academy, Ankara, Turkey

    Tarık Purtuloğlu

  3. Department of Pediatrics, GATA Medical Faculty, Haydarpasa Hospital, Istanbul, Turkey

    Gokhan Aydemir, Secil Aydinoz & Selami Süleymanoglu

Authors
  1. Ferhat Çekmez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tarık Purtuloğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gokhan Aydemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Secil Aydinoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kürşat Fidancı
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abdülbaki Karaoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Oğuzhan Babacan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fuat Emre Canpolat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Merih Çetinkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Turan Tunc
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Selami Süleymanoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ferhat Çekmez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Çekmez, F., Purtuloğlu, T., Aydemir, G. et al. Comparing beneficial effects of inhaled nitric oxide to l-arginine in necrotizing enterocolitis model in neonatal rats. Pediatr Surg Int 28, 1219–1224 (2012). https://doi.org/10.1007/s00383-012-3181-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-012-3181-8

Keywords

Search

Navigation