Pathogenesis and Detection of Oxygen Toxicity in the Newborn

  • R. M. W. Moison
  • A. A. Haasnoot
  • D. van Zoeren-Grobben
  • H. M. Berger
Conference paper


Reactive oxygen species (ROS) comprise a large variety of inorganic and organic oxygen-derived compounds, i.e., superoxide radical (∙O2), hydrogen peroxide (H2O2), hydroxyl radical (∙OH), hypochlorous acid (HOCl), nitric oxide radical (∙NO), and alkoxyl (RO∙), and peroxyl radicals (ROO∙; Gutteridge 1989). ∙NO reacts rapidly with ∙O2 to form the strong oxidant, the peroxynitrite anion (ONOO-) (Beckman et al. 1994).


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abman SH, Groothius JR (1994) Pathophysiology and treatment of bronchopulmonary dysplasia. Pediatr Clin North Am 41:277–315PubMedGoogle Scholar
  2. Beckman JS, Chen J, Ischiropoulos H, Crow JP (1994) Oxidative chemistry of peroxynitrite. Methods Enzymol 233:229–240PubMedCrossRefGoogle Scholar
  3. Berger HM, Lindeman JHN, van Zoeren-Grobben D et al. (1990) Iron overload, free radical damage, and rhesus haemolytic disease. Lancet 335:933–936PubMedCrossRefGoogle Scholar
  4. Berger HM, Moison RMW, van Zoeren-Grobben D (1994) The ins and outs of respiratory distress syndrome in babies and adults. JR Coll Physicians Lond 28:24–33Google Scholar
  5. Berger HM, Mumby S, Gutteridge JMC (1995) Ferrous ions detected in iron-overloaded cord blood plasma from preterm and term babies: implications for oxidative stress. Free Rad Res Comms (in press)Google Scholar
  6. Berry EM, Eisenberg S, Haratz D et al. (1991) Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins — the Jerusalem Nutrition Study: high MUFAs vs high PUFAs. Am J Clin Nutr 53:899–907PubMedGoogle Scholar
  7. Bonnes-Taourel D, Guérin MC, Toreilles J (1992) Is malonaldehyde a valuable indicator of lipid peroxidation? Biochem Pharmacol 44:985–988PubMedCrossRefGoogle Scholar
  8. Cao EH, Wang JJ (1993) Oxidative damage to DNA: levels of thymine glycol and thymidine glycol in neoplastic human urines. Carcinogenesis 14:1359–1362PubMedCrossRefGoogle Scholar
  9. Clahsen PC, Moison RMW, Holtzer CAJ, Berger HM (1992) Recycling of glutathione during oxidative stress in erythrocytes of the newborn. Pediatr Res 32:399–402PubMedCrossRefGoogle Scholar
  10. Corongiu FP, Banni S, Dessi MA (1989) Conjugated dienes detected in tissue lipid extracts by second derivative spectrophotometry. Free Rad Biol Med 7:183–186PubMedCrossRefGoogle Scholar
  11. Dennis KJ, Shibamoto T (1989) Gas chromatographic determination of malonaldehyde formed by lipid peroxidation. Free Rad Biol Med 7:187–192PubMedCrossRefGoogle Scholar
  12. Doelman CJA, Bast A (1990) Oxygen radicals in lung pathology. Free Rad Biol Med 9:381–400PubMedCrossRefGoogle Scholar
  13. Dorrepaal CA, Berger HM, Benders MJNL et al. (1995) Non-protein-bound iron in postasphyxiai reperfusion injury of the newborn. J Pediatr (submitted)Google Scholar
  14. Frank L (1992) Antioxidants, nutrition, and bronchopulmonary dysplasia. Clin Perinatol 19:541–562PubMedGoogle Scholar
  15. Frank L, Sosenko IRS (1987) Development of lung antioxidant enzyme system in late gestation: possible implications for the prematurely born infant. J Pediatr 110:9–14PubMedCrossRefGoogle Scholar
  16. Frank L, Sosenko IRS (1991) Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. Pediatr Res 29:292–296PubMedGoogle Scholar
  17. Frenkel K, Zhong Z, Wei H et al. (1991) Quantitative high-performance liquid chromatography analysis of DNA oxidized in vitro and in vivo. Anal Biochem 196:126–136PubMedCrossRefGoogle Scholar
  18. Frenkel K, Karkoszka J, Kim E, Taioli E (1993) Recognition of oxidized DNA bases by sera of patients with inflammatory diseases. Free Rad Biol Med 14:483–494PubMedCrossRefGoogle Scholar
  19. Gladstone IM, Levine RL (1994) Oxidation of proteins in neonatal lungs. Pediatrics 93:764–768PubMedGoogle Scholar
  20. Goldring C, Cassini AF, Maellaro E et al. (1993) Determination of 4-hydroxy-nonenal by high-performance liquid chromatography with electrochemical detection. Lipids 28:141–145PubMedCrossRefGoogle Scholar
  21. Grigg J, Arnon S, Silverman M (1992) Fractional processing of sequential bronchoalveolar lavage fluid from intubated babies. Eur Respir J 5:727–732PubMedGoogle Scholar
  22. Grigg J, Barber A, Silverman M (1993) Bronchoalveolar lavage fluid glutathione in intubated premature infants. Arch Dis Child 69:49–51PubMedCrossRefGoogle Scholar
  23. Gromisch DS, Lopez R, Cole HS, Cooperman JM (1977) Light (phototherapy)-induced riboflavin deficiency in the neonate. J Pediatr 90:118–122PubMedCrossRefGoogle Scholar
  24. Gutteridge JMC (1986) Antioxidant properties of the proteins caeruloplasmin, albumin and transferrin. A study of their activity in serum and synovial fluid from patients with rheumatoid arthritis. Biochem Biophys Acta 869:119–127PubMedCrossRefGoogle Scholar
  25. Gutteridge JMC, Halliwell B (1989) In: Free radicals in biology and medicine. Clarendon Press OxfordGoogle Scholar
  26. Gutteridge JMC (1991) Plasma ascorbate levels and inhibition of the antioxidant activity of caeruloplasmin. Clin Sci 81:413–417PubMedGoogle Scholar
  27. Gutteridge JMC, Quinlan GJ (1993) Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins. Biochim Biophys Acta 1156:144–150PubMedCrossRefGoogle Scholar
  28. Halliwell B, Chirico S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57715S–725SGoogle Scholar
  29. Halliwell B, Gutteridge JMC (1990) Antioxidants of human extracellular fluids. Arch Biochem Biophys 280:1–8PubMedCrossRefGoogle Scholar
  30. Helbock HJ, Motchnik PA, Ames BN (1993) Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants. Pediatrics 91:83–87PubMedGoogle Scholar
  31. Holm BA, Enhorning G, Notter NH (1988) A biophysical method by which plasma proteins inhibit lung surfactant activity. Chem Phys Lipids 49:49–55PubMedCrossRefGoogle Scholar
  32. Inder TE, Graham P, Sanderson K, Taylor BJ (1994) Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant. Arch Dis Child 70:F107–F111CrossRefGoogle Scholar
  33. Jacobs NJM, Drejer GF, Van Zoeren-Grobben D, Bindeis JG, Berger HM (1993) Long chain polyunsaturated fatty acids (LCP) in formula feeds and lipid peroxidation of red blood cells in the preterm baby. Abstract for the International Society for Free Radical Research Meeting SienaGoogle Scholar
  34. Jacobson W, Morley CJ, South M (1992) Microscopic observation on tracheal aspirates from ventilated neonates. II. The onset of bronchopulmonary dysplasia and other changes. Eur J Pediatr 151:204–207PubMedCrossRefGoogle Scholar
  35. Jobe AH (1991) Pathogenesis of respiratory failure in the preterm infant. Ann Med 23:687–691PubMedCrossRefGoogle Scholar
  36. Jones AF, Lunec J (1987) Protein fluorescence and its realtionship to free radical activity. BR J Cancer 55:60–65Google Scholar
  37. Kneepkens CMF, Lepage G, Roy CC (1994) The potential role of the hydrocarbon breath test as a measure of lipid peroxidation. Free Rad Biol Med 17:127–160PubMedCrossRefGoogle Scholar
  38. Lindeman JHN, van Zoeren-Grobben D, Schrijver J et al. (1989) The total free radical trapping ability of cord blood plasma in preterm and term babies. Pediatr Res 26:20–24PubMedCrossRefGoogle Scholar
  39. Lindeman JHN, Houdkamp E, Lentjes EGWM et al. (1992a) Limited protection against iron-induced lipid peroxidation by cord blood plasma. Free Rad Res Comms 16:285–294CrossRefGoogle Scholar
  40. Lindeman JHN, Lentjes EGWM, Houdkamp E et al. (1992b) Effect of an exchange transfusion on plasma antioxidants in the newborn. Pediatrics 90:200–203PubMedGoogle Scholar
  41. Michiels C, Remade J (1991) Cytotoxicity of linoleic acid peroxide, malondialdehyde and 4-hydroxynonenal towards human fibroblasts. Toxicology 66:225–234PubMedCrossRefGoogle Scholar
  42. Miyazawa T (1989) Determination of phospholipid hyeroperoxides in human blood plasma by a chemiluminescence-HPLC assay. Free Rad Biol Med 7:209–217PubMedCrossRefGoogle Scholar
  43. Moison RMW, Palinckx JJS, Roest M et al. (1993) Induction of lipid peroxidation of pulmonary surfactant by plasma of preterm babies. Lancet 341:79–82PubMedCrossRefGoogle Scholar
  44. Moison RMW, Van Zoeren-Grobben D, Haasnoot AA, Berger HM (1994) Early biochemical detection of bronchopulmonary dysplasia. Abstract for the International Society for Free Radical Research Meeting Sydney 1994Google Scholar
  45. Moison RMW, Van Hoof EJHA, Clahsen PC et al. (1995) Influence of plasma preparations and donor red blood cells on the antioxidant capacity of blood from newborn babies: an in vitro study. Acta Paediatr (submitted)Google Scholar
  46. Morrow JD, Hill KE, Burk RF et al. (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87:9383–9387PubMedCrossRefGoogle Scholar
  47. Németh I, Boda D (1994) Blood glutathione redox ratio as a parameter of oxidative stress in premature infants with IRDS. Free Rad Biol Med 16:347–353PubMedCrossRefGoogle Scholar
  48. Northway WH (1992) An introduction to bronchopulmonary dysplasia. Clin Perinatol 19:489–495PubMedGoogle Scholar
  49. Parker RA, Lindstrom DP, Cotton RB (1992) Improved survival accounts for most, but not all, of the increase in bronchopulmonary dysplasia. Pediatrics 90:663–668PubMedGoogle Scholar
  50. Phelps DL (1982) Neonatal oxygen toxicity — Is it preventable? Pediatr Clin North Am 29:1233–1240PubMedGoogle Scholar
  51. Pitkänen OM, Hallman M, Andersson SM (1990) Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants. J Pediatr 116:760–764PubMedCrossRefGoogle Scholar
  52. Robertson B (1992) Animal models of neonatal surfactant dysfunction. In: Robertson B, Van Golde LMG, Batenburg JJ (eds) Pulmonary surfactant: from molecular biology to clinical practice. Elsevier Science, Amsterdam, pp 459–484Google Scholar
  53. Schlenzig JS, Bervoets K, Loewenich V von, Böhles H (1993) Urinary malondialdehyde concentration in preterm neonates: is there a relationship to disease entities of neonatal intensive care? Acta Paediatr 82:202–205PubMedCrossRefGoogle Scholar
  54. Scott PH, Berger HM, Kenward C et al. (1975) Effect of gestational age and intrauterine nutrition on plasma trasnferrin and iron in the newborn. Arch Dis Child 50:796–798PubMedCrossRefGoogle Scholar
  55. Sosenko IRS, Frank L (1991) Nutritional influences on lung development and protection against chronic lung disease. Semin Perinatol 15:462–468PubMedGoogle Scholar
  56. Stadtman ER, Oliver CN (1991) Metal-catalyzed oxidation of proteins. J Biol Chem 266:2005–2008PubMedGoogle Scholar
  57. Toth KM, Clifford DP, Berger EM et al. (1984) Intact human erythrocytes prevent hydrogen peroxide-mediated damage to isolated perfused rat lungs and cultured bovine pulmonary artery endothelial cells. J Clin Invest 74:292–295PubMedCrossRefGoogle Scholar
  58. Toth KM, Berger EM, Beehler CJ, Repine JE (1986) Erythrocytes from cigarette smokers contain more glutathione and catalase and protect endothelial cells from hydrogen peroxide better than do erythrocytes from nonsmokers. Am Rev Respir Dis 134:281–284PubMedGoogle Scholar
  59. Uchida K, Kawakishi S (1993) 2-Oxo-histidine as a novel biological marker for oxidatively modified proteins. FEBS Lett 332:208–210PubMedCrossRefGoogle Scholar
  60. Van Asbeck BS, Hoidal J, Vercelotti GM et al. (1985) Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione. Science 227:756–759PubMedCrossRefGoogle Scholar
  61. Van Kuijk FJGM, Thomas DW, Stephens RJ, Dratz EA (1985) Gas chromatography — mass spectrometry method for determination of phospholipids. II. Transesterification to form penta-fluorobenzyl esters and detection with picogram sensitivity. Free Rad Biol Med 1:387–393CrossRefGoogle Scholar
  62. Van Zoeren-Grobben D, Schrijver J, Van den Berg H, Berger HM (1987) Human milk vitamin content after pasteurisation, storage or tube feeding. Arch Dis Child 62:161–165PubMedCrossRefGoogle Scholar
  63. Van Zoeren-Grobben D, Moison RMW, Ester WM, Berger HM (1993) Lipid peroxidation in human milk and infant formula: effect of storage, tube feeding and exposure to phototherapy. Acta Paediatr 82:645–649PubMedGoogle Scholar
  64. Van Zoeren-Grobben D, Lindeman JHN, Houdkamp E et al. (1994) Postnatal changes in plasma chain-breaking antioxidants in healthy preterm infants fed formula and/or human milk, Am J Clin Nutr 60:900–906PubMedGoogle Scholar
  65. Varsila E, Pitkänen O, Hallman M, Andesson S (1994) Immaturity-Dependent free radical activity in premature infants. Pediatr Res 36:55–59PubMedCrossRefGoogle Scholar
  66. Wayner DDM, Burton GW, Ingold KU et al. (1987) The relative contributions of vitamin E, urate ascorbate and proteins to the total radical trapping antioxidant activity of human blood plasma. Biochem Biophys Acta 924:408–419PubMedCrossRefGoogle Scholar
  67. Wickens DG, Norden AG, Lunec J, Dormandy TL (1983) Fluorescence changes in human gamma-globulin induced by free radical activity. Biochem Biophys Acta 742:607–616PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • R. M. W. Moison
  • A. A. Haasnoot
  • D. van Zoeren-Grobben
  • H. M. Berger

There are no affiliations available

Personalised recommendations