Am J Perinatol 2000; Volume 17(Number 04): 167-182
DOI: 10.1055/s-2000-9422
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

THE PRECARIOUS ANTIOXIDANT DEFENSES OF THE PRETERM INFANT

Donald W. Thibeault
  • Department of Pediatrics, Children's Mercy Hospital and The University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
Further Information

Publication History

Publication Date:
31 December 2000 (online)

ABSTRACT

Oxygen radicals are considered to be major causative factors in many illnesses of preterm infants. This article reviews the antioxidant defenses in immature animals and preterm infants, and attempts to quantitate their vulnerabilities to oxidants. Sources of oxidants, including hyperoxia, iron, parenteral nutrition, nitric oxide, and pro-oxidants, and their impact on immature antioxidant defenses are discussed. Genetic manipulations of antioxidant enzymes such as knockout and transgenic mice models are reviewed. The various clinical and investigational antioxidant therapies in animals and humans and difficulties in the design of antioxidant therapy studies are explored.

REFERENCES

  • 1 Su W Y, Folz R, Chen J S, Crapo J D, Chang L Y. Extracellular superoxide dismutase mRNA expressions in the human lung by in situ hybridization.  Am J Respir Cell Mol Biol . 1997;  16 162-170
  • 2 Folz R J, Guan J, Seldin M F, Oury T D, Enghild J J, Crapo J D. Mouse extracellular superoxide dismutase: primary structure, tissue-specific gene expression, chromosomal localization, and lung in situ hybridization.  Am J Respir Cell Biol . 1997;  17 393-403
  • 3 Folz R J, Guan J, Seldin M F. Immunocytochemical localization of extracellular superoxide dismutase in human lung.  Lab Invest . 1994;  70 889-898
  • 4 Oury T D, Chang L Y, Marklund S L, Day B J, Crapo J D. Immunocytochemical localization of extracellular superoxide dismutase in human lung.  Lab Invest . 1994;  70 889-897
  • 5 Karlsson K, Sandström J, Edlund A, Marklund S L. Turnover of extracellular-superoxide dismutase in tissues.  Lab Invest . 1994;  70 705-710
  • 6 Enghild J J, Crapo J D. Mouse extracellular superoxide dismutase: primary structure, tissue-specific gene expression, chromosomal localization, and lung in situ hybridization.  Am J Respir Cell Mol Biol . 1997;  17 392-403
  • 7 Carlsson L M, Jonsson J, Edlund T, Marklund S L. Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia.  Proc Natl Acad Sci . 1995;  92 6264-6268
  • 8 Oury T D, Ho Y S, Piantadosi C A, Crapo J D. Extracellular superoxide dismutase, nitric oxide and central nervous system O2 toxicity.  Proc Natl Acad Sci . 1992;  89 9715-9719
  • 9 Simonson S G, Welty-Wolf K E, Huang Y CT. Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry.  J Appl Physiol . 1997;  83 550-558
  • 10 Welty-Wolf K E, Simonson S G, Huang Y CT. Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometrics analysis.  J Appl Physiol . 1997;  83 559-568
  • 11 Omar B A, McCord J M. The cardioprotective effect of Mn-superoxide dismutase is lost at high doses in the postischemic isolated rabbit heart.  Free Rad Biol Med . 1990;  9 473-478
  • 12 Davis J M, Rosenfeld W N, Richter S E. Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.  Pediatrics . 1997;  100 24-30
  • 13 Davis J M, Rosenfeld W N, Sanders R J, Gonenne A. Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury.  J Appl Physiol . 1993;  74 2234-2241
  • 14 Rosenfeld W N, Davis J M, Parton L. Safety and pharmacokinetics of recombinant human superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.  Pediatrics . 1996;  97 811-817
  • 15 Davis J M, Rosenfeld W N, Richter S E. The effects of multiple doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome (RDS).  Pediatrics Res . 1999;  45 193A
  • 16 Keller G A, Warner T G, Steimer K S, Hallewell R A. Cu,Zn superoxide dismutase is a peroxismal enzyme in human fibroblasts and hepatoma cells.  Proc Natl Acad Sci . 1991;  88 7381-7385
  • 17 Frank L, Groseclose E E. Preparation for birth into an O2-rich environment: the antioxidant enzymes in the developing rabbit lung.  Pediatr Res . 1984;  75 569-574
  • 18 Gerdin E, Tyden O, Eriksson U J. The development of antioxidant enzymatic defense in the perinatal rat lung: activities of superoxide.  Pediatr Res . 1985;  18 240-244
  • 19 Tanswell A K, Freeman B A. Pulmonary antioxidant enzyme maturation in the fetal and neonatal rat. I. Developmental profiles.  Pediatr Res . 1984;  18 584
  • 20 Rickett G MW, Kelly F J. Developmental expression of antioxidant enzymes in guinea pig lung and liver.  Development . 1990;  108 331-336
  • 21 Frank L, Lewis P, Sosenko I RS. Dexamethasone stimulates fetal rat lung antioxidant enzyme activity in parallel with surfactant stimulation.  Pediatrics . 1985;  75 569-574
  • 22 Autor A P, Frank L, Roberts R J. Developmental characteristics of pulmonary superoxide dismutase: relationship to idiopathic respiratory distress syndrome.  Pediatr Res . 1976;  10 154-158
  • 23 Crapo J D, Tierney D F. Superoxide dismutase and pulmonary oxygen toxicity.  Am J Physiol . 1974;  226 1401-1407
  • 24 Laudert S, Thibeault D W, Rezaiekhaligh M M, Mabry S M, Huntrakoon M. Comparative age-related acute and chronic pulmonary oxygen tolerance in rats.  J Appl Physiol . 1994;  77 2709-2719
  • 25 Frank L, Iqbal J, Hass M, Massaro D. New ``rest period'' protocol for inducing tolerance to high O2 exposure in adult rats.  Am J Physiol . 1989;  257 L226-L231
  • 26 Saik L A, Hsieh H L, Baricos W H, Shapira E. Enzymatic and immunologic quantitation of erythrocyte superoxide dismutase in adults and in neonates of different gestational ages.  Pediatr Res . 1982;  16 933-937
  • 27 Clerch L B, Wright A E, Coalson J J. Lung manganese superoxide dismutase protein expression increases in the baboon model of bronchopulmonary dysplasia and is regulated at posttranscriptional level.  Pediatr Res . 1996;  39 253-258
  • 28 Kenney S E, Mathews M J, Rassin D K. Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration.  Pediatr Res . 1993;  33 177-18
  • 29 Sosenko I RS, Frank L. Guinea pig lung development: antioxidant enzymes and premature survival in high O2 .  Am J Physiol . 1987;  252 R693-R698
  • 30 Chen Y, Whitney P L, Frank L. Comparative responses of premature versus full-term newborn rats to prolonged hyperoxia.  Pediatr Res . 1994;  35 233-237
  • 31 Frank L, Sosenko I RS. Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits.  Pediatr Res . 1991;  29 292-296
  • 32 White C W, Ghezzi W P, Dinarello C A, Caldwell S A, McMurt I F, Repine J E. Recombinant tumor necrosis factor/cachectin and interleukin-1 pretreatment decreases lung oxidized glutathione accumulation, lung injury, and mortality in rats exposed to hyperoxia.  J Clin Invest . 1987;  79 1868-1873
  • 33 Wong G HW, Goeddel D F. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism.  Science . 1988;  242 941-944
  • 34 Visner G A, Dougall J M, Wilson J M, Burr I A, Nick H S. Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin 1, and tumor necrosis factor: role in the acute inflammatory response.  J Biol Chem . 1990;  265 2856-2864
  • 35 Tsan M F, White J E, Santana T A, Lee C Y. Tracheal insufflation of tumor necrosis factor protects rats against oxygen toxicity.  J Appl Physiol . 1990;  68 1211-1219
  • 36 Tsan M F. Superoxide dismutase and pulmonary oxygen toxicity.  Proc Soc Exp Biol Med . 1993;  203 286-290
  • 37 Shaffer J B, Treanor C P, DelVecchio P J. Expression of bovine and mouse endothelial cell antioxidant enzymes following TNF-α exposure.  Free Rad Biol Med . 1990;  8 497-502
  • 38 Ho Y-S, Dey M S, Crapo J D. Antioxidant enzyme expression in rat lungs during hyperoxia.  Am J Physiol . 1996;  270 L810-L818
  • 39 Kimball R E, Reddy K, Peirce T H, Schwartz L W, Mustafa M G, Cross C E. Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung.  Am J Physiol . 1976;  230 1425-1431
  • 40 Wispe J R, Warner B B, Clark J C. Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury.  J Biol Chem . 1992;  267 23937-23941
  • 41 Ho Y-S, Vincent R, Dey M S, Slot J W, Crapo J D. Transgenic models for the study of lung antioxidant defense: enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia.  Am J Respir Cell Mol Biol . 1998;  18 538-547
  • 42 White C W, Avraham K B, Shanley P F, Groner Y. Transgenic mice with expression of elevated levels of copper-zinc superoxide dismutase in the lungs are resistant to pulmonary oxygen toxicity.  J Clin Invest . 1991;  87 2162-2168
  • 43 White C W, Nguyen D-DH, Suzuki K. Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase.  Free Rad Biol Med . 1993;  15 629-636
  • 44 Tsan M-F, White J E, Caska B, Epstein C J, Lee C Y. Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity.  Am J Respir Cell Mol Biol . 1998;  19 114-120
  • 45 Li Y, Huang T T, Carlson E J. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase.  Nature Genet . 1995;  11 376-381
  • 46 Lebowitz R M, Zhang H, Vogel H. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice.  Proc Natl Acad Sci . 1996;  93 9782-9787
  • 47 Melov S, Coskun P, Patel M. Mitochondrial disease in superoxide dismutase 2 mutant mice.  Proc Natl Acad Sci . 1999;  96 846-851
  • 48 Walther F J, Gidding D EM, Kuipers I M. Prevention of oxygen toxicity with superoxide dismutase and catalase in premature lambs.  J Free Rad Biol Med . 1986;  2 289-293
  • 49 Thibeault D W, Rezaiekhaligh M, Mabry S. Lung antioxidant enzymes and cardiopulmonary responses in young rats exposed to hyperoxia and treated intratracheally with PEG catalase and superoxide dismutase.  Exp Lung Res . 1993;  19 137-151
  • 50 Turrens J F, Crapo J D, Freeman B A. Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.  J Clin Invest . 1984;  73 87-95
  • 51 Tanswell A K, Freeman B A. Liposome-entrapped antioxidant enzymes prevent lethal O2 toxicity in the newborn rat.  J Appl Physiol . 1987;  63 347-352
  • 52 Thibeault D W, Rezaiekhaligh M, Mabry S, Beringer T. Prevention of chronic pulmonary oxygen toxicity in young rats with liposome-encapsulated catalase administered intratracheally.  Pediatr Pulmonol . 1991;  11 318-327
  • 53 Michiels C, Raes M, Toussaint O, Remacle J. Importance of se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress.  Free Rad Biol Med . 1994;  17 235-248
  • 54 Karp W B, Robertson A F. Vitamin E in neonatology.  Adv Pediatr . 1986;  33 127-147
  • 55 Horwitt M K, Harvey C C, Dahm Jr C H, Searcy M T. Relationship between tocopherol and serum lipid levels for determination of nutritional adequacy.  Am J Acad Sci . 1972;  203 223-236
  • 56 Ritchie J H, Fish M B, McMaster V, Grossman M. Edema and hemolytic anemia in premature infants, a Vitamin E deficiency syndrome.  N Engl J Med . 1968;  279 1185-1190
  • 57 Oski F A, Barness L A. Vitamin E deficiency: a previously unrecognized cause of hemolytic anemia in the premature infant.  J Pediatr . 1967;  70 211-220
  • 58 Zipursky A, Brown E J, Watts J. Oral vitamin E supplementation for the prevention of anemia in premature infants: a controlled trial.  Pediatrics . 1987;  79 61-68
  • 59 Melhorn D, Gross S. Vitamin E-dependent anemia in the premature infant. II. Relationships between gestational age and absorption of Vitamin E.  J Pediatr . 1971;  79 581-588
  • 60 Böhles H. Antioxidative vitamins in prematurely and maturely born infants.  Int J Vit Nutr Res . 1997;  67 321-328
  • 61 Gutcher G R, Farrell P M. Early intravenous correction of vitamin E deficiency in premature infants.  J Pediatr Gastroenterol Nutr . 1985;  4 604-609
  • 62 Gutcher G R, Raynor W J, Farrell P M. An evaluation of Vitamin E status in premature infants.  Am J Clin Nutr . 1984;  40 1078-1089
  • 63 Phillips B, Franck L S, Greene H L. Vitamin E levels in premature infants during and after intravenous multivitamin supplementation.  Pediatrics . 1987;  80 680-683
  • 64 Kirksey A, Rahmanifar A. Vitamin and mineral composition of preterm human milk: implications for the nutritional management of the preterm infant. In: Berger H, ed. Vitamins and Minerals in Pregnancy and Lactation Nestlé Nutrition Workshop Series, Vol 16. New York: Nestec Ltd., Vevey/Raven Press, Ltd.; 1988
  • 65 Gilman A G, Goodman L S, Rall T W. Goodman and Gilman's The Pharmacological Basis of Therapeutics.  7th ed. New York: Macmillan Publishing Co; 1985
  • 66 Finer N N, Peters K L, Hayek Z. Vitamin E and necrotizing enterocolitis.  Pediatrics . 1984;  73 387-393
  • 67 Johnson L, Bowen F W, Abbasi S. Relationship of prolonged pharmacologic serum levels of Vitamin E to incidence of sepsis and necrotising enterocolitis in infants with birth weight 1500 grams or less.  Pediatrics . 1985;  75 619-638
  • 68 Law M R, Wijewardene K, Wald N J. Is routine Vitamin E administration justified in very low-birth weight infants?.  Dev Med Child Neurol . 1990;  32 442-450
  • 69 Amorde-Spalding K, D'Harlingue A E, Phillips B L. Tocopherol levels in infants greater than or equal to 1000 grams receiving MVI.  Pediatrics . 1992;  90 992-994
  • 70 Ehrenkranz R A, Mercurio M R. Bronchopulmonary dysplasia. In: Brackenm SJ, ed. Effective Care of the Newborn Infant New York: Oxford University Press 1992: 399-424
  • 71 Chiswick M L, Johnson M, Woodhall C. Protective effect of Vitamin E (DL-alpha-tocopherol) against intraventricular hemorrhage in premature babies.  Br Med J . 1983;  287 81-84
  • 72 Zachman R D. Retinol (Vitamin A) and the neonate: special problems of the human premature infant.  Am J Clin Nutr . 1989;  50 413-424.
  • 73 Shenai P, Chytil O F, Jhaveri A, Stahlman M T. Plasma Vitamin A and retinol-binding protein in premature and term neonates.  J Pediatr . 1981;  99 302-305
  • 74 Pearson E, Bose C, Snidow T. Trial of Vitamin A supplementation in very low birthweight infants at risk for bronchopulmonary dysplasia.  J Pediatr . 1992;  121 420-427
  • 75 Shenai J P, Chytil F, Stahlman M T. Liver vitamin A reserves of very-low-birth-weight neonates.  Pediatr Res . 1982;  16 177A
  • 76 Montreewasuwat N, Olson J A. Serum and liver concentrations of Vitamin A in Thai fetuses as a function of gestational age.  Am J Clin Nutr . 1979;  32 601
  • 77 Hustead V A, Gutcher G R, Anderson S A, Zachman R D. Relationship of Vitamin A (retinol) status to lung disease in the preterm infant.  J Pediatr . 1984;  105 610-615
  • 78 Gebre-Medhin M, Vahlquist A, Jofvander Y. Breast milk composition in Ethiopian and Swedish mothers.  Am J Clin Nutr . 1976;  29 441-451
  • 79 Rush M G, Shenai J P, Parker R A, Chytil F. Intramuscular versus enteral vitamin A supplementation in very low birth weight infants.  J Pediatr . 1994;  125 458-462
  • 80 Massaro G D, Massaro D. Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats.  Am J Physiol . 1996;  270 L305-L310
  • 81 Shenai J P, Chytil F, Stahlman M T. Vitamin A status of neonates with bronchopulmonary dysplasia.  Pediatr Res . 1985;  19 185-189
  • 82 Schwarz K B, Cox J M, Sharma S. Possible antioxidant effect of vitamin A supplementation in premature infants.  J Pediatr Gastro Nutr . 1997;  25 408-414
  • 83 Greene H L, Phillips B L, Franck L. Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion.  Pediatrics . 1987;  79 894-900
  • 84 Kennedy K A, Stoll B J, Ehrenkranz R A. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low?.  Early Hum Dev . 1997;  49 19-31
  • 85 Tyson J E, Wright L L, Oh W. Vitamin A supplementation for extremely-low-birth-weight infants.  N Engl J Med . 1999;  340 1962-1968
  • 86 Shenai J P. Vitamin A supplementation in very low birth weight neonates: rationale and evidence.  Pediatrics . 1000;  104 1369-1373
  • 87 Stocker R, Yamamoto Y, McDonagh A F, Glazer A N, Ames B N. Bilirubin is an antioxidant of possible physiological importance.  Science . 1987;  235 1043-1046
  • 88 Miller N J, Rice-Evans C, Davies M J, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates.  Clin Sci . 1993;  84 407-412
  • 89 Bélanger S, LaVoie J-C, Chessex P. Influence of bilirubin on the antioxidant capacity of plasma in newborn infants.  Biol Neonate . 1997;  71 233-238
  • 90 Hegyi T, Goldie E, Hiatt M. The protective role of bilirubin in oxygen-radical diseases of the preterm infant.  Perinatology . 1994;  XIV 296-300
  • 91 Dennery P A, McDonagh A F, Spitz D R, Rogers P A, Stevenson D K. Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia.  Free Rad Biol Med . 1995;  19 395-404
  • 92 Bolton C H, Leaf A A, Downs L G. Antioxidant defences and lipid peroxidation in preterm infants.  Biochem Soc Trans . 1997;  25 522S
  • 93 Benarson D A, Bowen F W. Variation of initial serum bilirubin rise in newborn infants with types of illness.  Lancet . 1991;  338 78-81
  • 94 Gaton D D, Gold J, Axer-Siegel R, Wielunsky E, Naor N, Nissenkorr I. Evaluation of bilirubin as possible protective factor in the prevention of retinopathy of prematurity.  Br J Ophthalmol. 1991;  75 532-534
  • 95 Frei B, England L, Amies B N. Ascorbate is an outstanding antioxidant in human blood plasma.  Proc Natl Acad Sci . 1989;  86 6377-6381
  • 96 Halliwell B. Vitamin C: Antioxidant or pro-oxidant in vivo?.  Free Rad Res . 1996;  25 439-454
  • 97 Cross C, Vandervliet A, Eiserich J, Wong T, Halliwell B. Oxidative stress and antioxidants in respiratory tract lining fluids. In: Clerch L, Massaro D, eds. Lung Biology in Health and Disease Oxygen, Gene Expression and Cellular Function New York: Marcel Dekker 1997: 367-388
  • 98 Halliwell B, Gutteridge J MC. Oxygen-free radicals and iron in relation to biology and medicine: some problems and concepts.  Arch Biochem Biophys . 1986;  246 501-514
  • 99 Sullivan J L. Iron, plasma antioxidants, and the oxygen radical disease of prematurity.  Am J Dis Child . 1988;  142 1341-1344
  • 100 Zhao G, Ayene I S, Fisher A B. Role of iron in ischemia-reperfusion oxidative injury of rat lungs.  Am J Respir Cell Mol Biol . 1997;  16 293-299
  • 101 Berger T M, Balz O F, Evans P H, Halliwell B, Morrow J. Does ascorbic acid and free iron in plasma of preterm infants cause oxidative damage?.  Pediatr Res . 1996;  195A 1156
  • 102 Berger H M, Mumby S, Gutteridge J MC. Ferrous ions detected in iron-overloaded cord blood plasma from preterm and term babies: Implications for oxidative stress.  Free Rad Res . 1995;  22 555-559
  • 103 Shah M, Bry K, Hallman M. Protective effect of exogenous transferrin against hyperoxia.  Pediatr Pulmonol . 1997;  24 429-437
  • 104 Gutteridge J MC. Plasma ascorbate levels and inhibition of the antioxidant activity of caeruloplasmin.  Clin Sci . 1991;  81 413-417
  • 105 Silvers K M, Gibson A T, Powers H J. High plasma Vitamin C concentrations at birth associated with low antioxidant status and poor outcome in premature infants.  Arch Dis Child . 1994;  71 F40-F44
  • 106 Bass W T, Malati N, Castle M C, White L E. Evidence for the safety of ascorbic acid administration to the premature infant.  Am J Perinatol . 1998;  15 133-140
  • 107 Deneke S M, Fanburg B L. Regulation of cellular glutathione.  Am J Physiol . 1989;  257 L163-173
  • 108 McCoy R N, Hill K E, Ayon M A, Stein J H, Burk R F. Oxidant stress following renal ischemia: changes in the glutathione redox ratio.  Kidney Int . 1988;  33 812-817
  • 109 Martensson J, Meister A. Glutathione deficiency decreases tissue ascorbate levels in newborn rats: ascorbate spares glutathione and protects.  Proc Natl Acad Sci . 1991;  88 4656-4660
  • 110 Smith C V, Hansen T N, Martin N E, McMicken H W, Elliott S J. Oxidant stress responses in premature infants during exposure to hyperoxia.  Pediatr Res . 1993;  34 360-365
  • 111 Jain A, Mehta T, Auld P AM. Glutathione metabolism in newborns: evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures.  Pediatr Pulmonol . 1995;  20 160-166
  • 112 Reise J A, Taylor G W, Fardy C H, Silverman M. Glutathione and neonatal lung disease.  Clinica Chimica Acta . 1997;  265 113-119
  • 113 Németh I, Boda D. Blood glutathione redox ratio as a parameter of oxidative stress in premature infants with IRDS.  Free Rad Biol Med . 1994;  16 347-353
  • 114 Saugstad O D. Role of xanthine oxidase and its inhibitor in hypoxia: reoxygenation injury.  Pediatrics . 1996;  98 103-107
  • 115 Quinlan G J, Lamb N H, Tilley R, Evans T W, Gutteridge J MC. Plasma hypoxanthine levels in ARDS: implications for oxidative stress, morbidity, and mortality.  Am J Respir Crit Care Med . 1997;  155 479-484
  • 116 Supnet M C, David-Cu R, Walther F J. Plasma xanthine oxidase activity and lipid hydroperoxide levels in preterm infants.  Pediatr Res . 1994;  36 283-287
  • 117 Roum J H, Borok Z, McElvaney N G. Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis.  J Appl Physiol . 1999;  87 438-443
  • 118 Cross C, Vandervliet A, Eiserich J, Wong T, Halliwell B. Oxidative stress and antioxidants in respiratory tract lining fluids. In: Clerch L, Massaro D, eds. Lung Biology in Health and Disease Oxygen, Gene Expression and Cellular Function New York: Marcel Dekker 1997: 367-388
  • 119 Nelly A, Finkelstein J N, Horowitz S. Extracellular glutathione peroxidase in human lung epithelial lining fluid and in lung cells.  Am J Physiol . 1996;  270 L173-182
  • 120 Brans Y W, Andrews D S, Carrillo D W, Dutton E P, Menchaca E M, Puleo-Scheppke B A. Tolerance of fat emulsions in very-low-birth-weight neonates.  Am J Dis Child . 1988;  142 145-152
  • 121 Heird W C, Gomez M R. Parenteral nutrition in low-birth-weight infants.  Annu Rev Nutr . 1996;  16 471-499
  • 122 Dhanireddy R, Hamosh M, Sivarubramanian K N. Postheparin lipolytic activity and intralipid clearance in very low birth weight infants.  J Pediatr . 1981;  98 617-622
  • 123 Dahms B B, Halpin T C. Pulmonary arterial lipid deposition in newborn infants receiving intravenous lipid infusion.  J Pediatr . 1980;  97 800-805
  • 124 Ogihara T, Kitagawa M, Miki M. Susceptibility of neonatal lipoproteins to oxidative stress.  Pediatr Res . 1991;  29 39-45
  • 125 Pironi L, Ruggeri E, Zolezzi C. Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition.  Am J Clin Nutr . 1998;  68 888-893
  • 126 Pitkänen O, Hallman M, Andersson S. Generation of free radicals in lipid emulsion used in parenteral nutrition.  Pediatr Res . 1991;  29 56-59
  • 127 Sosenko I, Rodriguez-Pierce M, Bancalari E. Effect of early initiation of intravenous lipid administration on the incidence and severity of chronic lung disease in premature infants.  J Pediatr . 1993;  123 975-982
  • 128 Hammerman C, Aramburo M. Decreased lipid intake reduces morbidity in sick premature neonates.  J Pediatr . 1988;  113 1083-1088
  • 129 Brownlee K G, Kelly E J, Ng P C, Kendall-Smith S C, Dear P RF. Early or late parenteral nutrition for the sick preterm infant?.  Arch Dis Child . 1993;  69 281-283
  • 130 Gilbertson N, Kovar I Z, Cox D J, Crowe L, Palmer N T. Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate.  J Pediatr . 1991;  119 615-623
  • 131 Helbock H H, Ames B N. Use of intravenous lipids in neonates.  J Pediatrics . 1995;  126 747-748
  • 132 Helbock H, Motchnik P, Ames B. Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants.  Pediatrics . 1993;  91 83-88
  • 133 Neuzil J, Darlow B, Inder T, Sluis K, Winterbourn C, Stocker R. Oxidation of parenteral lipid emulsion by ambient and phototherapy lights: potential toxicity of routine parenteral feedings.  J Pediatr . 1995;  126 785-790
  • 134 Steger P JK, Mühlebach S F. Lipid peroxidation of IV lipid emulsions in TPN bags: the influence of tocopherols.  Nutrition . 1998;  14 179-185
  • 135 Greene H L, Hazlett D, Demaree R. Relationship between intralipid induced hyperlipidemia and pulmonary function.  Am J Clin Nutr . 1976;  29 127
  • 136 Hertel J, Tystrup I, Andersen G E. Intravascular fat accumulation after intralipid infusion in the very low-birth-weight infant.  J Pediatr . 1982;  100 975-976
  • 137 Lloyd T R, Boucek M M. Effect of Intralipid on the neonatal pulmonary bed: an echocardiographic study.  J Pediatr . 1986;  108 130-133
  • 138 Levene M I, Wigglesworth J S, Desal R. Pulmonary fat accumulation after Intralipid infusion in the preterm infant.  Lancet . 1980;  11 815-818
  • 139 Teague W G, Raj J U, Braun D, Berner M E, Clyman R I, Bland R D. Lung vascular effects of lipid infusion in awake lambs.  Pediatr Res . 1987;  22 714-719
  • 140 Schröder H, Paust H, Schmidt R. Pulmonary fat embolism after Intralipid therapy: a post-mortem artefact?.  <~>Light and electron microscopic investigations in low-birth-weight infants. Acta Pediatr . 1984;  73 461-464
  • 141 Cook R. Factors associated with chronic lung disease in preterm infants.  Arch Dis Child . 1991;  66 776-770
  • 142 Strunk R C, Murrow B W, Thilo E, Kunke K S, Johnson E G. Normal macrophage function in infants receiving Intralipid by low-dose intermittent administration.  J Pediatr . 1985;  106 640-646
  • 143 Fischer F W, Hunter K W, Wilson S R, Mease A D. Diminished bacterial defences with Intralipid.  Lancet . 1980;  819-820
  • 144 Recalde A L, Nickerson B G, Vegas M, Scott C B, Landing B H, Warburton D. Lipid-laden macrophages in tracheal aspirates of newborn infants receiving intravenous lipid infusions: a cytologic study.  Pediatr Pathol . 1984;  2 25-34
  • 145 Avila-Figueroa C, Goldmann D A, Richardson D K, Gray J E, Ferrari A, Freeman J. Intravenous lipid emulsions are the major determinant of coagulase-negative staphylococcal bacteremia in very low birth weight newborns.  Pediatr Infect Dis J . 1998;  17 10-17
  • 146 Lavoie J C, Bélanger S, Spalinger M, Chessex P. Admixture of a multivitamin preparation to parenteral nutrition: the major contributor to in vitro generation of peroxides.  Pediatrics . 1997;  99 e6
  • 147 Brawley V, Bhatia J, Karp W B. Hydrogen peroxide generation in a model pediatric parenteral amino acid solution.  Clin Sci . 1993;  85 709-712
  • 148 Bhatia J, Stegink L D, Ziegler E E. Riboflavin enhances photo-oxidation of amino acids under simulated clinical conditions.  J Parenter Enter Nutr . 1983;  7 277-279
  • 149 Bhatia J, Mims L C, Roesel R A. The effect of phototherapy on amino acid solutions containing multivitamins.  J Pediatr . 1980;  96 284-286
  • 150 Shattuck K E, Bhatia J, Grinnell C, Rassin D K. The effects of light exposure on the in vitro hepatic response to an amino acid-vitamin solution.  J Parenter Enter Nutr . 1995;  19 398-402
  • 151 Gromisch D S, Lopez R, Cole H S, Cooperman J M. Light (phototherapy)-induced riboflavin deficiency in the neonate.  J Pediatr . 1977;  90 118-122
  • 152 Gebicki S, Gebicki J M. Formation of peroxides in amino acids and proteins exposed to oxygen free radicals.  Biochem J . 1993;  289 743-749
  • 153 Stranak Z, Zabrodsky V, Simak J. Changes in alveolar-arterial oxygen difference and oxygenation index during low-dose nitric oxide inhalation in 15 newborns with severe respiratory insufficiency.  Eur J Pediatr . 1996;  155 907-910
  • 154 O'Donnell V B, Chumley P H, Hogg N, Bloodworth A, Darley-Usmar V M, Freeman B A. Nitric oxide inhibition of lipid peroxidation: kinetics of reaction with lipid peroxyl radicals and comparison with alpha-tocopherol.  Biochemistry . 1997;  36 15216-15223
  • 155 Collet-Martin S, Gatecel C, Kermarrec N, Gougerot-Pocidalo M A, Payen D. Alveolar neutrophil functions and cytokine levels in patients with the adult respiratory distress syndrome during nitric oxide inhalation.  Am J Respir Crit Care Med . 1996;  153 985-990
  • 156 Ekekezie I I, Thibeault D W, Zwick D L. Independent and combined effects of prolonged inahled nitric oxide and oxygen on lung inflammation in newborn piglets.  Biol Neonate . 2000;  77 37-44
  • 157 Gessler P, Nebe T, Birle A, Mueller W, Kachel W. A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: functional impairment of the neutrophil respiratory burst.  Intensive Care Med . 1996;  22 252-258
  • 158 Lamb N J, Quinlan G J, Westerman S T, Gutteridge J MC, Evan T W. Nitration of proteins in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome receiving inhaled nitric oxide.  Am J Respir Crit Care Med . 1999;  160 1031-1034
  • 159 Banks B A, Ischiropoulos H, McClelland M, Ballard P L, Ballard R A. Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia.  Pediatrics . 1998;  101 870-874
  • 160 Banks B A, Seri I, Ischiropoulos H, Merrill J, Rychik J, Ballard R A. Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia.  Pediatr . 1999;  103 610-618
  • 161 Matalon S, DeMarco V, Haddad I Y. Inhaled nitric oxide injures the pulmonary surfactant system of lambs in vivo.  Am J Physiol . 1996;  270 L273-L280
  • 162 Robbins C G, Davis J M, Merritt T A. Combined effects of nitric oxide and hyperoxia on surfactant function and pulmonary inflammation.  Am J Physiol . 1995;  269 L545-L550
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