title: Ascorbylperoxide from parenteral nutrition induces an increase of redox potential of glutathione and loss of alveoli in newborn guinea pig lungs.
abstract: BACKGROUND
  Bronchopulmonary dysplasia is one of the main complications associated with extreme prematurity. Oxidative stress is suspected to be a trigger event of this lung disease, which is characterized by impaired alveolar development. Peroxides, mainly ascorbylperoxide and H2O2, are known contaminant of parenteral nutrition. We hypothesize that these oxidant molecules induce bronchopulmonary dysplasia development. The aim was to determine if the infusion of ascorbylperoxide, whether in presence or absence of H2O2, is associated with oxidative stress, apoptosis and loss of alveoli in the lungs of newborn guinea pigs.
  
  
  METHODS
  Three-day-old guinea pigs received parenteral solutions containing 0, 20, 60 or 180 µM ascorbylperoxide in the presence or not of 350 µM H2O2 (concentrations similar to those measured in parenteral nutrition). After 4 days, the lungs were collected for determination of glutathione's redox potential, caspase-3 activation (an apoptosis marker), alveolarization index (by histology), activation of Nrf2 and NF?B (biological markers of oxidative stress), and IL-6 and PGJ2 levels (markers of NF?B activation). Groups were compared by ANOVA, p < 0.05.
  
  
  RESULTS
  Loss of alveoli was associated with ascorbylperoxide in a dose-dependent manner, without an influence of H2O2. The dose-dependent activation of caspase-3 by ascorbylperoxide was lower in the presence of H2O2. Ascorbylperoxide induced an increase of redox potential in a dose-dependent manner, which reached a plateau in presence of H2O2. Nrf2 and NF?B were activated by H2O2 but not by ascorbylperoxide.
  
  
  CONCLUSIONS
  Results suggest that ascorbylperoxide, generated in parenteral nutrition, is involved in the development of bronchopulmonary dysplasia, independently of the increase of the redox potential. This study underlines the importance of developing a safer formulation of parenteral nutrition.
authors.affiliation: Departments of Pediatrics and Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5.
authors.forename: Wesam
authors.initials: W
authors.lastname: Elremaly
authors.affiliation: Departments of Pediatrics and Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mohamed
authors.affiliation: Departments of Pediatrics and Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Mialet-Marty
authors.affiliation: Departments of Pediatrics and Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Rouleau
authors.affiliation: Departments of Pediatrics and Nutrition, CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada H3T 1C5.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lavoie
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000633:toxicity; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010288:Parenteral Nutrition; D010545:Peroxides / Q000633:toxicity*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000032:analysis; D011650:Pulmonary Alveoli / Q000503:physiopathology*
chemical_list: D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D010545:Peroxides; C550723:ascorbylperoxide; C037112:9-deoxy-delta-9-prostaglandin D2; D006861:Hydrogen Peroxide; D053148:Caspase 3; D005978:Glutathione; D001205:Ascorbic Acid; D015230:Prostaglandin D2
keywords: Bronchopulmonary dysplasia; Chronic lung disease; Glutathione; Oxidative stress; Premature newborn