Advertisement

Neonatology pp 242-249 | Cite as

Oxygen Toxicity

  • Giuseppe Buonocore
  • Rodolfo Bracci
  • Serafina Perrone
  • Maximo Vento

Abstract

Although the use of oxygen in the care of newborns dates since the eighteenth century [1] and the toxic effects of oxygen had been mentioned already at the end of the 19th century [2], the first evidence of a relationship between oxygen toxicity and neonatal diseases emerged in the early 1950s when retinopathy was observed in premature infants breathing high concentrations of oxygen [3]. At about the same time, the red cells of newborns were demonstrated to have increased susceptibility to oxygen damage [4]. Great advances in our understanding of toxic effects of oxygen were made in the years that followed, when oxygen toxicity was recognized to be due to the development of reactive oxygen species (ROS). The main ROS are the superoxide anion (O 2 ), hydrogen peroxide (H2O2), lipid peroxide (LOOH), peroxyl radicals RO 2 · and the hydroxyl radical (OH·). Other important radicals are the highly reactive electron delocalized phenoxyl radical (C6H5O) and nitric oxide (NO) [4]. The term ROS includes free radicals, which are atoms or molecules with one or more unpaired electrons. A free radical can be defined as any molecule capable of independent existence with one or more unpaired electrons. In addition, ROS encompasses molecules that can be defined as free radicals (e.g., anion superoxide) and others that are oxidizing species, relative to molecular O2 but do not possess an unpaired electron (e.g., hydrogen peroxide) [5]. Free radicals may react with other radicals, the unpaired electrons forming a covalent bond. The resulting molecule may decompose other molecules into toxic products. Free radicals may react with non-radical molecules in free radical chain reactions, which are stopped by antioxidant molecules, enzymes or protein reactions. Superoxide anion [O 2 ] is the precursor of most ROS and a mediator in oxidative chain reactions. Dismutation of O 2 by superoxide dismutase SOD) produces H2O2 which in turn may be fully reduced to water by glutathione peroxidase (GSH-Px) and catalase (Cat) or partially reduced to hydroxyl radical [OH·]. The latter reaction is called the Fenton-Haber Weiss reaction and is catalyzed by reduced transition metals, particularly iron, but also copper and zinc [6]. There is no specific scavenger for this radical and, once released, OH· reacts with lipoproteins, cell membranes, lipids, proteins, DNA, amino acids and other molecules causing structural and functional damage to theses structures. Since the OH· is formed by the so called Fenton reaction which is dependent on non protein bound iron (NPBI), the conditions of intracellular or extracellular availability of NPBI is one of the most important source of ROS dependent tissue damage. Oxidative tissue damage may also be mediated by reactive nitroxide species [6]. The reaction product of NO and O 2 is the unstable molecule peroxynitrite (ONOO) which is regarded as highly reactive [6].

Keywords

Reactive Oxygen Species Reactive Oxygen Species Production Preterm Infant Oxygen Toxicity Advanced Oxidation Protein Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Chaussier F. Paris, Histoire de la Société Royale de Médecine 1780–1981, vol 4, pp 346–354Google Scholar
  2. 2.
    Smith JL (1899) The pathological effects due to increase of oxygen tension in the air breathed. J Physiol 24:19–35PubMedGoogle Scholar
  3. 3.
    Patz A, Hoeck I, de la Cruz E (1952) Studies on the effect of high oxygen administration in retrolental fibroplasia. Am J Ophthalmol 35:1248–1253PubMedGoogle Scholar
  4. 4.
    Gordon HH, Nitowsky HM, Cornblath M (1955) Studies of tocopherol deficiency in infants and children. I. Hemolysis of erythrocytes in hydrogen peroxide. Am J Dis Child 90:669–681Google Scholar
  5. 5.
    Jankov RP, Negus A, Tanswell AK (2001) Antioxidants as therapy in the newborn: some words of caution. Pediatr Res 50:681–687PubMedCrossRefGoogle Scholar
  6. 6.
    Halliwell B, Gutteridge JMC, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 1:598–620Google Scholar
  7. 7.
    Ullrich V, Bachscmid M (2000) Superoxide as a messenger of endothelial function. Biochem Biophys Res Commun 278:1–8PubMedCrossRefGoogle Scholar
  8. 8.
    Koenig JM, Yoder MC (2004) Neonatal neutrophils: the good, the bad and the ugly. Clin Perinatol 31:39–51PubMedCrossRefGoogle Scholar
  9. 9.
    Sies H (1991) Role of reactive oxygen species in biological processes. Klin Wochenschr 69:965–968PubMedCrossRefGoogle Scholar
  10. 10.
    Halliwell B (2007) Biochemitry of oxidative stress. Biochem Soc Trans 35:1147–1150PubMedCrossRefGoogle Scholar
  11. 11.
    Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13PubMedCrossRefGoogle Scholar
  12. 12.
    Grisham MB (2004) Reactive oxygen species in immune responses. Free Radic Biol Medicine 36:1479–1480CrossRefGoogle Scholar
  13. 13.
    Ginsburg I, Kohen R (1995) Cell damage in inflammatory and infectious sites might involve a coordinated “cross-talk” among oxidants, microbial haemolysis and ampiphiles, cationic proteins, phospholipases, fatty acids, proteinases and cytokines (an overview). Free Rad Res 22:489–517CrossRefGoogle Scholar
  14. 14.
    Grisham, MB, Hernandez LA, Granger DN (1986) Xanthine oxidase and neutrophil infiltration intestinal ischemia. Am J Physiol 251:G567–G574PubMedGoogle Scholar
  15. 15.
    Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313PubMedCrossRefGoogle Scholar
  16. 16.
    Delivoria-Papadopoulos M, Mishra OP (2000) Mechanisms of perinatal cerebral injury in fetus and newborn. Ann N Y Acad Sci 900:159–168PubMedCrossRefGoogle Scholar
  17. 17.
    Saugstad OD (2005) Oxidative stress in the newborn-A 30-year perspective. Biol Neonate 88:228–236PubMedCrossRefGoogle Scholar
  18. 18.
    Chandel NS, Shumacker PT (2000) Cellular oxygen sensing by mitochondria: old question, new insight. J Appl Physiol 88:1880–1889PubMedCrossRefGoogle Scholar
  19. 19.
    Chang E, Hornick K, Fritz KI et al (2007) Effects of hyperoxia on cortical neuronal nuclear function and programmed cell death mechanism. Neurochem Res 32:1142–1149PubMedCrossRefGoogle Scholar
  20. 20.
    Li JM, Shah AM (2004) Endothelial cell superoxide generation:regulation and relevance for cardiovascular pathophysiology. Am J Physiol Integr Comp Physiol 287:R1014–R1030CrossRefGoogle Scholar
  21. 21.
    Frank L, Sosenko IRS (1987) Prenatal development of lung antioxidant enzymes in four species. J Pediatr 110:106–110PubMedCrossRefGoogle Scholar
  22. 22.
    Gross RT, Bracci R, Rudolph N et al (1967) Hydrogen peroxide toxicity and detoxification in the erythrocytes of newborn infants. Blood 29:481–493PubMedGoogle Scholar
  23. 23.
    Frank L, Sosenko IRS (1987) Prenatal development of lung antioxidant enzymes in four species. J Pediatr 110:106–110PubMedCrossRefGoogle Scholar
  24. 24.
    Friel JK, Friesen RW, Harding SV, Roberts LJ (2004) Evidence of oxidative stress in full-term healthy infants. Pediatr Res 56:878–882PubMedCrossRefGoogle Scholar
  25. 25.
    Tiina MA, Kari OR, Mika S, Vuokko LK (1998) Expression and development profile of antioxidant enzymes in human lung and liver. Am J Respir Cell Mol Biol 19:942–949Google Scholar
  26. 26.
    Comporti M, Signorini C, Leoncini S et al (2004) Plasma F2-isoprostanes are elevated in newborns and inversely correlated to gestational age. Free Radic Biol Med 37:724–732PubMedCrossRefGoogle Scholar
  27. 27.
    House JT, Schultetus RR, Gravenstein N (1987) Continuous neonatal evaluation in the delivery room by pulse oximetry. J Clin Monit 3:96–100PubMedCrossRefGoogle Scholar
  28. 28.
    Vento M, Asensi M, Sastre J et al (2002) Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants. Semin Perinatol 26:406–410PubMedCrossRefGoogle Scholar
  29. 29.
    Forman HJ, Fukuto JM, Miller T et al (2008) The chemistry of cell signalling by reactive oxygen species and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys 477:183–195PubMedCrossRefGoogle Scholar
  30. 30.
    Martín JA, Pereda J, Martínez-López I et al (2007) Oxidative stress as a signal to up-regulate gamma-cystathionase in the fetalto-neonatal transition in rats. Cell Mol Biol (Noisy-le-grand) 53 (Suppl):OL1010–1017Google Scholar
  31. 31.
    Asikainen TM, White CW (2004) Pulmonary antioxidant defenses in the preterm newborn with respiratory distress and bronchopulmonary dysplasia in evolution: implications for antioxidant therapy. Antioxid Redox Signal 6:155–167PubMedCrossRefGoogle Scholar
  32. 32.
    Halliday H (2008) Surfactant, past, present and future. J Perinatol 28(Suppl 1):S47–S56PubMedCrossRefGoogle Scholar
  33. 33.
    Vento M, Aguar M, Escobar JJ et al (2009) Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. Antioxid Redox Signal 11:2945–2955PubMedCrossRefGoogle Scholar
  34. 34.
    Rogers S, Witz G, Anwar M et al (2000) Antioxidant capacity and oxygen radical diseases in the preterm newborn. Arch Pediatr Adolesc 154:544–548Google Scholar
  35. 35.
    Njålsson R, Norgren S (2005) Physiological and pathological aspects of GSH metabolism. Acta Paediatr 94:132–137PubMedCrossRefGoogle Scholar
  36. 36.
    Yeung MY (2006) Influence of early postnatal nutritional management on oxidative stress and antioxidant defence in extreme prematurity. Acta Paediatr 95:153–163PubMedCrossRefGoogle Scholar
  37. 37.
    Smith CV, Hansen TN, Martin NE et al (1993) Oxidant stress responses in premature infants during exposure to hyperoxia. Pediatr Res 34:360–365PubMedCrossRefGoogle Scholar
  38. 38.
    Viña J, Vento M, Garcia-Sala F et al (1995) L-Cysteine and glutathione metabolism are impaired in premature infants due to a cystathionase deficiency. Am J Clin Nutr 61:1067–1069PubMedGoogle Scholar
  39. 39.
    Halliwell B, Gutteridge JMC (1990) The antioxidants of human extracellular fluids. Arch Biochem Biophys 280:1–8PubMedCrossRefGoogle Scholar
  40. 40.
    Buonocore G, Perrone S, Bracci R (2001) Free radicals and brain damage in the newborn. Biol Neonate 79:180–186PubMedCrossRefGoogle Scholar
  41. 41.
    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 22:555–559CrossRefGoogle Scholar
  42. 42.
    Lindeman JHN, Lentjes EG, van Zoeren-Grobben D et al (2000) Postnatal changes in plasma ceruloplasmin and transferrin antioxidant activies in preterm babies. Biol Neonate 78:73–76PubMedCrossRefGoogle Scholar
  43. 43.
    Evans PJ, Evans P, Kovar IZ et al (1992) Bleomycin-detectable iron in the plasma of premature and full-term neonates. FEBS Lett 303:210–212PubMedCrossRefGoogle Scholar
  44. 44.
    Marzocchi B, Perrone S, Paffetti P et al (2005) Non protein bound and plasma protein oxidant stress at birth. Pediatr Res 58:1–5CrossRefGoogle Scholar
  45. 45.
    Signorini C, Perrone S, Sgherri C (2008) Plasma esterified F2-Isoprostanes and oxidative stress in newborns: Role of non protein bound iron. Pediatr Res 63:287–291PubMedCrossRefGoogle Scholar
  46. 46.
    Buonocore G, Perrone S, Longini M et al (2003) Non protein bound iron as early predictive marker of neonatal brain damage. Brain 126:1224–1230PubMedCrossRefGoogle Scholar
  47. 47.
    Buonocore G, Perrone S, Longini M et al (2000) Total hydroperoxide and advanced oxidation protein products in preterm hypoxic babies. Pediatr Res 47:221–224PubMedCrossRefGoogle Scholar
  48. 48.
    Buonocore G, Perrone S, Longini M (2002) Oxidative stress in preterm neonate at birth and on seventh day of life. Pediatr Res 52:46–49PubMedGoogle Scholar
  49. 49.
    Longini M, Perrone S, Kenanidis A et al (2005) Isoprostanes in amniotic fluid: a predictive marker for fetal growth restriction in pregnancy. Free Radic Biol Med 38:1537–1541PubMedCrossRefGoogle Scholar
  50. 50.
    Bracci R, Buonocore G (2003) Chorioamnionitis: A risk factor for fetal and neonatal morbidity. Biol Neonate 83:85–96PubMedCrossRefGoogle Scholar
  51. 51.
    Frank L (1991) Developmental aspects of experimental pulmonary oxygen toxicity. Free Radic Biol Med 11:463–494PubMedCrossRefGoogle Scholar
  52. 52.
    Vento M, Aguar M, Escobar J et al (2009) Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. Antioxid Redox Signal 11:2945–2955PubMedCrossRefGoogle Scholar
  53. 53.
    Asikainen TM, Raivio KO, Saksela M, Kinnula VL (1998) Expression and developmental profile of antioxidant enzymes in human lung and liver. Am J Respir Cell Mol Biol 19:942–949PubMedGoogle Scholar
  54. 54.
    Vento M, Moro M, Escrig R et al (2009) Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 124:439–449CrossRefGoogle Scholar
  55. 55.
    Denis D, Fayon MJ, Berger P et al (2001) Prolonged moderate hyperoxia induced hyperresponsiveness and airway inflammation in newborn rats. Pediatr Res 50:515–519PubMedCrossRefGoogle Scholar
  56. 56.
    Bhandari V (2008) Molecular mechanism of hyperoxia induced acute lung injury. Front Biosc 13:6653–6661CrossRefGoogle Scholar
  57. 57.
    Appleby C, Towner RA (2001) Magnetic resonance imaging of pulmonary damage in the term and premature rat neonate exposed to hyperoxia. Pediatr Res 50:502–507PubMedCrossRefGoogle Scholar
  58. 58.
    Kotecha S, Chan B, Azam N et al (1995) Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease. Arch Dis Child 72:F90–F96CrossRefGoogle Scholar
  59. 59.
    Buonocore G, Zani S, Perrone S et al (1998) Intraerythrocyte non protein bound iron and plasma malondialdehyde in the hypoxic newborn. Free Radic Biol Med 25:766–770PubMedCrossRefGoogle Scholar
  60. 60.
    Ciccoli L, Rossi V, Leoncini S et al (2004) Iron release, superoxide production and binding of autologous IgG to band 3 dimers in newborn and adult erythrocytes exposed to hypoxia and hypoxia-reoxygenation. Biochim Biophys Acta 1672:203–213PubMedCrossRefGoogle Scholar
  61. 61.
    Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture:how shoul you do it and what do the resuls mean? Brit J Pharmacol 142:231–253CrossRefGoogle Scholar
  62. 62.
    Mikami T, Kita K, Tomita S et al (2000) Is allantoin in serum and urine a useful indicator of excerse-induced oxidative stress in humans? Free Rad Res 32:235–244CrossRefGoogle Scholar
  63. 63.
    Drury JA, Jeffers G, Cooke RW (1998) Urinary 8-hydroxydeoxyguanosine in infants and children. Free Radic Res 28:423–428PubMedCrossRefGoogle Scholar
  64. 64.
    Eiserich JP, Hristova M, Cross CE et al (1998) Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391:393–397PubMedCrossRefGoogle Scholar
  65. 65.
    Lubec G, Widness JA, Hayde M et al (1997) Hydroxyl radical generation in oxygen-treated infants. Pediatrics 100:700–704PubMedCrossRefGoogle Scholar
  66. 66.
    Solberg R, Andresen JH, Escrig R et al (2007) Resuscitation of hypoxic newborn piglets with oxygen induces a dose dependent increase in markers of oxidative stress. Pediatr Res 62:559–563PubMedCrossRefGoogle Scholar
  67. 67.
    Ledo A, Arduini A, Asensi MA et al (2009) Human milk enhances antioxidant defenses against hydroxyl radical aggression in preterm infants. Am J Clin Nutr 89:210–215PubMedCrossRefGoogle Scholar
  68. 68.
    Chow LC, Wright KW, Sola A et al (2003) Can changes in clinical pratice decrease the incidence of severe retinopathy of prematurity in very low birth weight infants? Pediatrics 111:339–345PubMedCrossRefGoogle Scholar
  69. 69.
    Tin W, Gupta S (2007) Optimum oxygen therapy in preterm babies. Arch Dis Child Fetal Neonatal Ed 92:F143–F147PubMedCrossRefGoogle Scholar
  70. 70.
    Sun SC (2002) Relation of target Sp O2 levels and clinical outcome in ELBW infants on supplemental oxygen. Pediatr Res 51:A350Google Scholar
  71. 71.
    Schulze A, White K, Way RC et al (1995) Effect of the arterial oxygenation level on cardiac output, oxygen extraction, and oxygen comsumption in low birth weight infants receiving mechanical ventilation. J Pediatr 126:777–784PubMedCrossRefGoogle Scholar
  72. 72.
    Poets C, Arand J, Hummler H et al (2003) Retinopathy of prematurity: a comparison between two centers aiming for different pulse oximetry saturation levels. Biol Neonate 84:A267Google Scholar
  73. 73.
    Askie LM, Henderson-Smart DJ (2004) Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants. Cochrane Database Syst Rev 4:CD001077Google Scholar
  74. 74.
    Askie LM, Handerson-Smart OJ, Ko H (2008) Restricted versus liberal oxygen exposure for preventive morbidity and mortality in preterm or low birth weight infants. Cochrane Database Syst Rev 1:CD001077Google Scholar
  75. 75.
    Wolkoff LI, Narula P (2000) Issue in neonatal and pediatric oxygen therapy. Respir Care Clin N Am 6:675–691PubMedCrossRefGoogle Scholar
  76. 76.
    Friel JK, Martin SM, Langdon M et al (2002) Milk from mothers of both premature and full-term infants provides better antioxidant protection than does infant formula. Pediatr Res 51:612–618PubMedCrossRefGoogle Scholar
  77. 77.
    Aycicek A, Erel O, Kocyigit A et al (2006) Breast milk provides better antioxidant power than does formula. Nutrition 22:616–619PubMedCrossRefGoogle Scholar
  78. 78.
    Ledo A, Arduini A, Asensi MA et al (2009) Human milk enhances antioxidant defenses against hydroxyl radical aggression in preterm infants. Am J Clin Nutr 89:210–215PubMedCrossRefGoogle Scholar
  79. 79.
    Buonocore G, Groenendal F (2007) Antioxidant strategy. Semin Fetal Neonatal Med 12:287–295PubMedCrossRefGoogle Scholar
  80. 80.
    Tan DX, Chen LD, Poeggeler B et al (1993) Melatonin: A potent, endogenous hydroxyl radical scavenger. Endocrine J 1:57–66Google Scholar
  81. 81.
    Gitto E, Reiter RJ, Cordaro SP et al (2004) Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am J Perinatol 21:209–216PubMedCrossRefGoogle Scholar
  82. 82.
    Gitto E, Karbownik M, Reiter RJ et al (2001) Effects of melatonin treatment in septic newborns. Pediatr Res 50:756–760PubMedCrossRefGoogle Scholar
  83. 83.
    Carloni S, Perrone S, Buonocore G (2008) Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J Pineal Res 44:157–164PubMedCrossRefGoogle Scholar
  84. 84.
    Brion LP, Bell EF, Raghuveer TS (2003) Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev 3:CD003665PubMedGoogle Scholar
  85. 85.
    Silvers KM, Sluis KB, Darlow BA et al (2001) Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid. Acta Pediatr 90:242–249CrossRefGoogle Scholar
  86. 86.
    Italian Collaborative Group on Preterm Delivery (1991) Absorption of intramuscular vitamin E in premature babies. Dev Pharmacol Ther 16:13–21Google Scholar
  87. 87.
    Pitkanen OM, Luukkainen P, Andersson S (2004) Attenuated lipid peroxidation in preterm infants during subsequent doses of intravenous lipids. Biol Neonate 85:184–187PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Giuseppe Buonocore
    • 1
  • Rodolfo Bracci
  • Serafina Perrone
  • Maximo Vento
  1. 1.Department of Pediatrics, Obstetrics and Reproductive Medicine Division of NeonatologyUniversity of SienaSienaItaly

Personalised recommendations