Depletion of pulmonary glutathione using diethylmaleic acid accelerates the development of oxygen-induced lung injury in term and preterm guinea-pig neonates.
Dietary or chemical depletion of pulmonary glutathione in adult rats and mice, has been demonstrated to exacerbate the toxic effects of high oxygen concentrations. The present paper has examined this phenomenon in a guinea-pig model of prematurity, using the electrophilic agent diethylmaleic acid (DEM) to provide a transient (up to 12 h) pulmonary glutathione depletion. Full-term and 3-days preterm guinea-pig pups were studied to assess the possible role for glutathione deficiency as a mechanism mediating the increased susceptibility of the immature lung to oxygen free-radical damage. The administration of DEM to guinea-pig neonates depleted lung glutathione by 90% (term) or 68% (preterm) over 2 h. On exposure of pups to 95% oxygen for 48 h, DEM increased the incidence of oxygen-related death to 31% in term pups and 100% in preterm pups. Term pups exposed to hyperoxia and treated with DEM showed evidence of pulmonary injury, indicated by an influx of neutrophils into the lung airspaces, and elevated microvascular permeability. Control pups exposed to 95% oxygen were found to have uninjured lungs after 48 h. We conclude that glutathione is an essential component of the pulmonary antioxidant array in neonates. Glutathione may be of particular importance in the early phase of oxygen exposure. The deficiency of lung glutathione observed in preterm animals may account for their increased susceptibility to oxygen-induced pulmonary injury.
Department of Human Nutrition, University of Southampton, UK.
S C
SC
Langley
F J
FJ
Kelly
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D010100:Oxygen / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects
D008298:Maleates; C014476:diethyl maleate; D005978:Glutathione; D010100:Oxygen