Skip to main content

Advertisement

SpringerLink
Log in

Increased heme oxygenase-1 expression in premature infants with respiratory distress syndrome

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Oxidative stress is known to play an important role in the pathogenesis of certain severe illnesses in preterm infants. The enzyme heme oxygenase-1 (HO-1) participates in cytoprotection against oxygen radical injury. We have previously described the role of HO-1 in physiologic adaptation by demonstrating the induction of HO-1 in healthy mature neonates and asymptomatic preterm infants. Our current aim was to investigate the HO-1 expression in preterm infants with respiratory distress syndrome (RDS). We collected venous blood samples from 28 preterm infants with RDS on the 1st, 3rd and 5th days after birth. The HO-1 mRNA expression was determined by means of a competitive reverse transcriptase PCR technique, and a quantitative blood count was performed on the residual blood sample. A significant increase in HO-1 expression was found in the preterm infants with RDS as compared with both the healthy mature and the asymptomatic premature groups. The elevation was approximately eight-fold. The platelet count displayed a significant negative association with the HO-1 expression, and in the RDS prematures with thrombocytopenia the HO-1 induction was significantly greater than in those with a normal platelet count. In conclusion, the RDS of prematures is accompanied by an elevated HO-1 expression during the first 5 days of life, consistent with the inflammatory and oxidative characteristics of the disease.

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

Similar content being viewed by others

Abbreviations

a/A :

arterio-alveolar oxygen ratio

cRT-PCR:

competitive reverse transcriptase polymerase chain reaction

HCT:

hematocrit

HGB:

hemoglobin

HO-1:

heme oxygenase-1

PLT:

platelet

RDS:

respiratory distress syndrome

WBC:

white blood cell

References

  1. Ainsworth SB (2005) Pathophysiology of neonatal respiratory distress syndrome: implications for early treatment strategies. Treat Respir Med 4:423–437

    Article  PubMed  Google Scholar 

  2. Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Eaton JW, Balla G (2005) Heme, heme oxygenase and ferritin in vascular endothelial cell injury. Mol Nutr Food Res 49:1030–1043

    Article  PubMed  CAS  Google Scholar 

  3. Benaron DA, Bowen FW (1991) Variation of initial serum bilirubin rise in newborn infants with type of illness. Lancet 338:78–81

    Article  PubMed  CAS  Google Scholar 

  4. Brus F, van Oeveren W, Okken A, Oetomo SB (1997) Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity. Pediatrics 99:672–680

    Article  PubMed  CAS  Google Scholar 

  5. Chakravorty S, Murray N, Roberts I (2005) Neonatal thrombocytopenia. Early Hum Dev 81:35–41

    Article  PubMed  Google Scholar 

  6. Dani C, Martelli E, Bertini G, Pezzati M, Filippi L, Rossetti M, Rizzuti G, Rubaltelli FF (2003) Plasma bilirubin level and oxidative stress in preterm infants. Arch Dis Child Fetal Neonatal Ed 88:F119–F123

    Article  PubMed  CAS  Google Scholar 

  7. Dani C, Masini E, Bertini G, di Felice AM, Pezzati M, Ciofini S, Rossetti M, Gallori G, Ciuti R, Buonocore G, Paffetti P, Mannaioni PF, Rubaltelli FF (2004) Role of heme oxygenase and bilirubin in oxidative stress in preterm infants. Pediatr Res 56:873–877

    Article  PubMed  CAS  Google Scholar 

  8. Fujita T, Toda K, Karimova A, Yan SF, Naka Y, Yet SF, Pinsky DJ (2001) Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 7:598–604

    Article  PubMed  CAS  Google Scholar 

  9. Israels SJ, Rand ML, Michelson AD (2003) Neonatal platelet function. Semin Thromb Hemost 29:363–372

    Article  PubMed  CAS  Google Scholar 

  10. Krediet TG, Cirkel GA, Vreman HJ, Wong RJ, Stevenson DK, Groenendaal F, Egberts J, Van Bel F (2006) End-tidal carbon monoxide measurements in infant respiratory distress syndrome. Acta Paediatr 95:1075–1082

    Article  PubMed  Google Scholar 

  11. Lindenblatt N, Bordel R, Schareck W, Menger MD, Vollmar B (2004) Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo. Arterioscler Thromb Vasc Biol 24:601–606

    Article  PubMed  CAS  Google Scholar 

  12. Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2:2557–2568

  13. Maroti Z, Katona M, Orvos H, Nemeth I, Farkas I, Turi S (2007) Heme oxygenase-1 expression in premature and mature neonates during the first week of life. Eur J Pediatr 166:1033–1038

    Article  PubMed  CAS  Google Scholar 

  14. Morse D, Choi AM (2005) Heme oxygenase-1: from bench to bedside. Am J Respir Crit Care Med 172:660–670

    Article  PubMed  Google Scholar 

  15. Mumby S, Upton RL, Chen Y, Stanford SJ, Quinlan GJ, Nicholson AG, Gutteridge JM, Lamb NJ, Evans TW (2004) Lung heme oxygenase-1 is elevated in acute respiratory distress syndrome. Crit Care Med 32:1130–1135

    Article  PubMed  CAS  Google Scholar 

  16. Nemeth I, Boda D (1994) Blood glutathione redox ratio as a parameter of oxidative stress in premature infants with IRDS. Free Radic Biol Med 16:347–353

    Article  PubMed  CAS  Google Scholar 

  17. Nupponen I, Pesonen E, Andersson S, Makela A, Turunen R, Kautiainen H, Repo H (2002) Neutrophil activation in preterm infants who have respiratory distress syndrome. Pediatrics 110:36–41

    Article  PubMed  Google Scholar 

  18. O’Donovan DJ, Fernandes CJ (2004) Free radicals and diseases in premature infants. Antioxid Redox Signal 6:169–176

    Article  PubMed  CAS  Google Scholar 

  19. Otterbein LE, Choi AM (2000) Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 279:L1029–L1037

    PubMed  CAS  Google Scholar 

  20. Otterbein LE, Soares MP, Yamashita K, Bach FH (2003) Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol 24:449–455

    Article  PubMed  CAS  Google Scholar 

  21. Rogers S, Witz G, Anwar M, Hiatt M, Hegyi T (2000) Antioxidant capacity and oxygen radical diseases in the preterm newborn. Arch Pediatr Adolesc Med 154:544–548

    PubMed  CAS  Google Scholar 

  22. Sedlak TW, Snyder SH (2004) Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics 113:1776–1782

    Article  PubMed  Google Scholar 

  23. Thibeault DW (2000) The precarious antioxidant defenses of the preterm infant. Am J Perinatol 17:167–181

    Article  PubMed  CAS  Google Scholar 

  24. van Bel F, Latour V, Vreman HJ, Wong RJ, Stevenson DK, Steendijk P, Egberts J, Krediet TG (2005) Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome? J Appl Physiol 98:1044–1049

    PubMed  Google Scholar 

  25. Wagener FA, Volk HD, Willis D, Abraham NG, Soares MP, Adema GJ, Figdor CG (2003) Different faces of the heme-heme oxygenase system in inflammation. Pharmacol Rev 55:551–571

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Szeged, Korányi fasor 14-15, Szeged, H-6720, Hungary

    Ildikó Farkas, Zoltán Maróti, Márta Katona, Emőke Endreffy, Péter Monostori, Krisztina Máder & Sándor Túri

Authors
  1. Ildikó Farkas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zoltán Maróti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Márta Katona
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emőke Endreffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Péter Monostori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Krisztina Máder
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sándor Túri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ildikó Farkas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Farkas, I., Maróti, Z., Katona, M. et al. Increased heme oxygenase-1 expression in premature infants with respiratory distress syndrome. Eur J Pediatr 167, 1379–1383 (2008). https://doi.org/10.1007/s00431-008-0673-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-008-0673-6

Keywords

Search

Navigation