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Revista Portuguesa de Pneumologia

versão impressa ISSN 0873-2159

Rev Port Pneumol v.14 n.1 Lisboa fev. 2008

 

Stress oxidativo na lesão pulmonar neonatal

Oxidative stress in the neonatal lung disease

 

Gustavo Rocha 1

 

Resumo

O stress oxidativo é um dos factores de risco para o desenvolvimento de displasia broncopulmonar no recém--nascido de pré-termo. Este apresenta deficiente defesa antioxidante. Por outro lado, o stress oxidativo também tem papel no crescimento e desenvolvimento celular. A relação entre stress oxidativo e crescimento celular necessita de ser melhor conhecida antes da introdução de terapêuticas antioxidantes. Várias terapêuticas antioxidantes têm sido tentadas, até ao momento sem êxito. Neste artigo é feita uma revisão da evidência do papel dos radicais livres de oxigénio na displasia broncopulmonar.

Palavras-chave: Displasia broncopulmonar, defesa antioxidante, recém-nascido de pré-termo, stress oxidativo.

 

 

Abstract

Oxidative stress is a risk factor for bronchopulmonary dysplasia in the preterm newborn. Antioxidant defense is impaired in the preterm newborn. Oxidative stress is also involved in cell growth and development. The relationship between oxidative stress and cell growth needs to be understood before antioxidant therapy can be routinely introduced. Several antioxidant therapies have been unsuccessfully tried until now. This review highlights the importance of oxygen free radicals in the pathogenesis of bronchopulmonary dysplasia.

Key-words: Bronchopulmonary dysplasia, antioxidant defense, preterm infant, oxidative stress.

 

Texto completo disponível apenas em PDF.

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Bibliografia

 

1. Campbell K. Intensive oxygen therapy as a possible cause of retrolental fibroplasia: a clinical approach. Med J Aust 1950; 2:48-50.         [ Links ]

2. Frank L, Bucher JR, Roberts RJ. Oxygen toxicity in neonatal and adult animals of various species. J Appl Physiol 1978; 45:699-704.

3. Frank L, Groseclose EE. Preparation for birth into a O 2 -rich environment: the antioxidant enzymes in the developing rabbit lung. Pediatr Res 1988; 18:501-4.

4. Saugstad OD. Hypoxanthine as an indicator of hypoxia: its role in health and disease through free radical production. Pediatr Res 1988; 23:143-50.

5. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163:1723-9.

6. Jobe AH. The new bronchopulmonary dysplasia: an arrest of lung development. Pediatr Res 1999; 46:641-3.

7. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet 2006; 29:1421-31.

8. Coalson JJ. Pathology of chronic lung disease of early infancy. In: Bland RD, Coalson JJ (Eds.). Chronic Lung Disease of Early Infancy. New York: Marcel Dekker, 2000: 85-124.

9. Abman SH. Pulmonary hypertension in chronic lung disease of infancy. Pathogenesis, pathophysiology and treatment. In: Chronic Lung Disease of Infancy. Bland RD, Coalson JJ (Eds.). New York: Marcel Dekker, 2000: 619-68.

10. Greenough A, Alexander J, Burguess S. Health care utilisation of prematurely born, preschool children related to hospitalisation for RSV infection. Arch Dis Child 2004; 89:673-8.

11. Koumbourlis AC, Motoyama EK, Mutich RL, Mallory GB, Walczak SA, Fertal K. Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with chronic lung disease. Pediatr Pulmonol 1996; 21:28-34.

12. Wilborn AM, Evers LB, Canada AT. Oxygen toxicity to the developing lung of the mouse: role of reactive oxygen species. Pediatric Res 1996; 40:225-32.

13. Han RN, Buch S, Tseu I, Young J, Christie NA, Frndova H, et al. Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen. Pediatr Res 1996; 39:921-9.

14. Saugstad OD. Bronchopulmonary dysplasia – oxidative stress and antioxidants. Semin Neonatol 2003; 8:39-49.

15. Zoban P, Cerny M. Immature lung and acute lung injury. Physiol Res 2003; 52:507-16.

16. Zweir JL, Duke SS, Kuppusamy P. Electron paramagnetic resonance evidence that cellular oxygen toxicity is caused by generation of superoxide and hydroxy free radicals. FEBS Lett 1989; 252:12-6.

17. Freeman BA, Crapo JD. Hyperoxia increases oxygen free radical production in rat lung mitichondria. J Biol Chem 1981; 256:10986-92.

18. Freeman BA, Topolsky MK, Crapo JD. Hyperoxia increases oxygen radical production in rat lung homogenates. Arch Biochem Biophys 1982; 216:477-84.

19. Turrens JF, Freeman BA, Crapo JD. Hyperoxia increases H 2 O 2 release by lung mitochondria and microsomes. Arch Biochem Biophys 1982; 217:411-21.

20. Yusa T, Crapo JD, Freeman BA. Hyperoxia enhances lung and liver nuclear superoxide generation. Biochim Biophys Acta 1984; 793:167-74.

21. Kinsella JP, parker TA, galan, Sheridan BC, Halbower AC, Abman SH. Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease. Pediatr Res 1997; 41:457-63.

22. Ter Horst SA, walther FJ, Poorthuis BJ, Hiemstra PS, Wagenaar GT. Inhaled nitric oxide attenuates pulmonary inflammation and fibrin deposition and prolongs survival in neonatal hyperoxic lung injury. Am J Physiol Lung Cell Mol Physiol 2007; 23: [Epub ahead of print].

23. Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BL, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999; 181:773-9.

24. Auten RL, Mason SN, Whorton MH, Lampe WR, Foster WM, Goldberg RN, et al. Inhaled ethyl nitrite prevents hyperoxia-impaired postnatal alveolar development in newborn rats. Am J Respir Crit Care Med 2007; 3: [Epub ahead of print].

25. Frank L. Development of the antioxidant defenses in fetal life. Semin Neonatol 1998; 3:173-82.

26. Transwell AK, Freeman BA. Pulmonary antioxidant enzyme maturation in the fetal and neonatal rat. I. Developmental profiles. Pediatr Res 1984; 18:240-4.

27. Gerdin E, Tyden O, Eriksson UJ. The development of antioxidant enzymatic defense in the perinatal rat lung: activities of superoxide dismutase, glutathione peroxidase, and catalase. Pediatr Res 1985; 19:687-91.

28. Walther FJ, Wade AB, Warburton D. Ontogeny of antioxidant enzymes in the fetal lamb lung. Exp Lung Res 1991; 17:39-45.

29. Frank L, Sosenko IRS. Prenatal development of lung antioxidant enzymes in four species. J Pediatr 1987; 110:106-10.

30. Frank L, Sosenko IRS. Development of lung antioxidant enzyme in late gestation: possible implications for the prematurely-born infant. J Pediatr 1987; 110:9-14.

31. Frank L. Antioxidants, nutrition, and bronchopulmonary dysplasia. In: Holtzman RB, Frank L (Eds.). Bronchopulmonary Dysplasia. Clinics in Perinatology 1992; 19:541-62.

32. Autor AP, Frank L, Roberts RJ. Developmental characteristics of pulmonary superoxide dismutase: relationship to idiopathic respiratory distress syndrome. Pediatr Res 1976; 19:154-8.

33. Rooney SA. The surfactant system and lung phospholipids biochemistry. Am Rev Respir Dis 1985; 131:439-60.

34. Bancalari E. Pathogenesis of bronchopulmonary dysplasia: an overview. In: Bancalari E, Stocket JT(Eds.). Bronchopulmonary Dysplasia. Washington: Hemisphere, 1998: 3-15.

35. Vina J, Vento M, Garcia Sala F, Puertes IR, Gasco E, Sastre J, et al. L-cysteine and glutathione metabolism are impaired in premature infants due to cystathione deficiency. Am J Clin Nutr 1995; 61:1067-9.

36. Pallardo FV, Sastre J, Asensi M. Physiological changes in glutathione metabolism in foetal and newborn rat liver. Biochem J 1991; 15; 247:891-3.

37. Phylactos AC, Leaf AA, Costeloe K, Crawford MA. Erythrocyte cupric/zinc superoxide dismutase exhibits reduced activity in preterm and low birthweight infants at birth. Acta Paediatr 1995; 84:1421-5.

38. Thibeult DW. The precarious antioxidant defenses of the preterm infant. Am J Perinatol 2000; 17:167-81.

39. Frank L, Sosenko IRS. Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rats. Pediatr Res 1991; 29:292-6.

40. Hudak BB, Egan EA. Impact of lung surfactant therapy on chronic lung disease in premature infants. Clinics in Perinatology 1992; 19:591-602.

41. Hustead VA, Gutcher GR, Anderson SA. Relationship of vitamin A (retinol) status to lung disease in the preterm infant. J Pediatr 1984; 105:610-5.

42. Gutcher GR, Reynor WJ, Farrel PM. An evaluation of vitamin E status in premature infants. Am J Clin Nutri 1984; 40:1078-89.

43. Huijbers WAR, Schrijvers J, Speek AJ. Persistent low plasma vitamin E in premature infants surviving respiratory distress syndrome. Eur J Pediatr 1986; 145:170-1.

44. Omene JA, Longe AC, Ihongbe JC. Decreased umbilical cord serum ceruloplasmin concentrations in infants with hyaline membrane disease. J Pediatr 1981; 99:136-8.

45. Rosenfeld W, Concepcion L, Evans H. Serial trypsin inhibitory capacity and ceruloplasmin levels in prematures at risk for bronchopulmonary dysplasia. Am Rev Respir Dis 1986; 134:1229-32.

46. Walravens PA. Nutritional importance of copper and zinc in neonates and infants. Clin Chem 1980; 26:185-9.

47. Van Caille-Bertand M, Degenhart HJ, Fernandes J. Selenium status of infants on nutritional support. Acta Paed Scand 1984; 73:816-21.

48. Rosenfeld W. Clinical evidence of oxidant injury in bronchopulmonary dysplasia. In: Bancalari E, Stocker JT (Eds.). Bronchopulmonary Dysplasia. Washington: Hemisphere, 1988; 42-8.

49. Bonikos DS, Bensch KG. Pathogenesis of bronchopulmonary dysplasia. In: Merritt TA, Northway Jr WH, Boynton BR (Eds.). Bronchopulmonary Dysplasia. Boston: Blackwell, 1988: 33-58.

50. Kelly FJ, Lubec J. Hyperoxide injury of immature guinea pig lung is mediated via hydroxyl radicals. Pediatr Res 1995; 38:286-91.

51. Clerch LB, Wright AE, Coalson JJ. Lung manganese superoxide dismutase protein expression increases in the baboon model of bronchopulmonary dysplasia and is regulated at a posttranscriptional level. Pediatr Res 1996; 39:253-8.

52. Moison RM, de Beaufort AJ, Haasnot AA, Dubbelman TM, van Zoeren-Grobben D, Berger HM. Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease. Free Radic Biol Med 1997; 23:226-34.

53. Ogihara T, Okamoto R, Kim H-S, Nagai A, Morinobu T, Moji H, et al. New evidence for the involvement of oxygen radicals in triggering neonatal chronic lung disease. Pediatr Res 1996; 39:117-9.

54. Lubec G, Widness JA, Hayde M, Menzel D, Pollak A. Hydroxyl radical generation in oxygen-treated infants. Pediatrics 1997; 100:700-4.

55. Schock BC, Sweet DG, Halliday HL, Young IS, Ennis M. Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease. Am J Physiol Lung Cell Mol Physiol 2001; 281:L 1386-91.

56. Creuwels LAJM, van Golde LMG, Haagsman HP. The pulmonary surfactant system: biochemical and clinical aspects. Lung 1997; 175:1-39.

57. Wright JR. Immunomodulatory functions of surfactant. Physiol Rev 1997; 77:931-62.

58. Haagsman HP. Oxidative damage of the pulmonary surfactant system. Semin Neonatol 1998; 3:207-17.

59. Oostig RS, Van Iwaarden JF, van Bree L. Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells. Am J Physiol 1992; 262:L63-L68.

60. Haagsman HP, Schuurmans EAJM, Batenbur JJ. Synthesis of phosphatidylcholines in ozone-exposed alveolar type II cells isolated from adult rat lung: is glycerolphosphate acyltransferase a rate-limiting enzyme? Exp Lung Res 1988; 14:1-17.

61. Gladstone IM, Levine RL. Oxidation of proteins in neonatal lungs. Pediatrics 1994; 93:764-8.

62. Varsila E, Pesonem E, Andersson S. Early protein oxidation in the neonatal lung is related to development of chronic lung disease. Acta Paediatr 1995; 84:1296-9.

63. Varsila E, Pitkanen O, Hallman M, Andersson S. Immaturity dependent free radical activity in premature infants. Pediatr Res 1994; 36:55-9.

64. Varsila E, Hallman M, Andersson S. Free-radicalinduced lipid peroxidation during the early neonatal period. Acta Paediatr 1994; 83:692-5.

65. Pitkanen OM, Hallman M, Andersson SM. Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birthweight infants. J Pediatr 1990; 116:760-4.

66. Inder TE, Graham P, Sanderson K, Taylor BJ. Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant. Arch Dis Child Fetal Neonatal Ed 1994; 70:F 101-11.

67. Ogihara T, Hirnao K, Morinobu T, Kim H-S, Hiroi M, Ogihara H, et al. Raised concentration of dehyde lipid peroxidation products in premature infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 1999; 80: F 21-5.

68. Dik W, De Krijger RR, Bonecamp L, Naeber BAE, Zimmermann JI, Versneh MA. Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia. Pediatr Res 2001; 50:761-6.

69. Sweet DG, McMahon KJ, Curley AG, O´Connor CM, Halliday HL. Type 1 collagenases in bronchoalveolar lavage fluid from preterm babies at risk of developing chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2001; 84:F 168-71.

70. Cerederquist K, Sorsa T, Tervahantiala T, Maisi P, Reunanen K, Lassus P, et al. Matrix metalloproteinases-2,-8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 2001; 108:686-92.

71. Welty SE. Is there a role for antioxidant therapy in bronchopulmonary dysplasia? J Nutr 2001; 131:947S-50S.

72. Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, et al. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 1999; 340:1962-8.

73. Watts JL, Milner R, Zipursky A, Paes B, Ling E, Gill G et al. Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. Eur Respir J 1991; 4:188-90.

74. Padmanabhan RV, Gudapaty R, Liener IE, Schwartz   BA, Hoidal JR. Protection against pulmonary oxygen toxicity in rats by intratracheal administration of liposome-encapsulated superoxide dismutase or catalase. Am Rev Respir Dis 1985; 132:164-7.

75. Saugstad OD, Halman M, Becher G, Oddoy A, Lachmann B. Respiratory failure caused by intratracheal saline: additive effect of xanthine oxidase. Biol Neonate 1988; 54:61-7.

76. Saugstad OD, Becher G, Grossman M, Oddoy A Merker G, Lachmann B. Acute and chronic lung damage in guinea pigs induced by xanthine oxidase. Intensive Care Med 1987; 13:30-2.

77. Davis JM. Superoxido dismutase: a role in the prevention of chronic lung disease. Biol Neonate 1998; 74 (suppl 1):29-34.

78. Davis JM, Richter SE, Biswas S, Rosenfeld WN, Parton L, Gewolb IH, et al. Long term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase. J Perinatol 2000; 20:213-6.

79. Davis JM. Role of oxidant injury in the pathogenesis of neonatal lung disease. Acta Paediatr Suppl 2002; 437:23-5.

80. Suresh GK, Davis JM, Soll RF. Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants. Cochrane Database Syst Rev 2001; 1:CD 001968.

81. Bany-Mohammed FM, Slivka S, Hallman M. Recombinant human erythropoietin: possible role as antioxidant in premature rabbits. Pediatr Res 1996; 40:381-7.

82. Russell GAB, Cooke RWI. Randomised controlled trial of allopurinol prophilaxis in very preterm infants. Arch Dis Child Fetal Neonatal Ed 1995; 73:F27-31.

83. Ahola T, Lapatto R, Raivio KO, Selander D, Stigson L, Jonsson B, et al. N-acetylcystein (NAC) does not prevent bronchopulmonary dysplasia (BPD) in extremely low birth weight infants (ELBEI). Pediatric Academic Societies Lecture; 2002.

84. Collard KJ, Godeck S, Holley JE, Quinn MW. Pulmonary antioxidant concentrations and oxidative damage in ventilated premature babies. Arch Dis Child Fetal Neonatal Ed 2004; 89:F 412-6.

 

 

1 Assistente Hospitalar, Serviço de Neonatologia. Unidade Autónoma de Gestão da Mulher e da Criança, Hospital de São João, Porto. Faculdade de Medicina da Universidade do Porto

Correspondência: Gustavo Rocha

Serviço de Neonatologia

Unidade Autónoma de Gestão da Mulher e da Criança

Hospital de São João – Piso 2

Alameda Prof. Hernâni Monteiro

4202 - 451 Porto

Telefone: 22 551 21 00 ext: 1949

Fax: 22 551 22 73 / 22 502 57 66

E-mail: gusrocha@oninet.pt

 

Recebido para publicação/received for publication: 07.06.01

Aceite para publicação/accepted for publication: 07.07.31