title: Cyclooxygenase-2 inhibition partially protects against 60% O2 -mediated lung injury in neonatal rats.
abstract: BACKGROUND
  Use of the anti-inflammatory agent dexamethasone in premature infants with bronchopulmonary dysplasia has been curtailed, and no alternative anti-inflammatory agents are approved for this use. Our objective was to use a neonatal rat model of bronchopulmonary dysplasia to determine if an highly selective cyclooxygenase-2 inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU; 10 µg/g body weight), could prevent inflammatory cell influx and protect against lung injury.
  
  
  METHODS
  Neonatal rats exposed to air or 60% O2 for 14 days from birth either received daily i.p. injections of (i) vehicle or DFU or (ii) vehicle or an EP(1) receptor antagonist, SC-19220.
  
  
  RESULTS
  DFU attenuated the lung macrophage and neutrophil influx, prevented interstitial thickening and prevented the loss of peripheral blood vessels induced by 60% O2 , but did not protect against the variance in alveolar diameter induced by 60% O2 . Exposure to 60% O2 caused both an increase in lung prostaglandin E2 content and a reduction in lung mesenchymal cell mass which was reversed by DFU. Prostaglandin E2 binding to the EP(1) receptor inhibited DNA synthesis in cultures of lung fibroblasts in a dose dependent fashion. Treatment with SC-19220 attenuated the reduction in lung mesenchymal mass observed following exposure of rat pups to 60% O2 .
  
  
  CONCLUSIONS
  An highly selective cyclooxygenase-2 inhibitor is an effective anti-inflammatory substitute for dexamethasone for preventing phagocyte influx into the neonatal lung during 60% O2 -mediated lung injury, and can modify the severity of that injury.
authors.affiliation: Lung Biology Programme, Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Azhar
authors.initials: A
authors.lastname: Masood
authors.forename: Man
authors.initials: M
authors.lastname: Yi
authors.forename: Mandy
authors.initials: M
authors.lastname: Lau
authors.forename: Rosetta
authors.initials: R
authors.lastname: Belcastro
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Crystal
authors.initials: C
authors.lastname: Kantores
authors.forename: Cecil R
authors.initials: CR
authors.lastname: Pace-Asciak
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jankov
authors.forename: A Keith
authors.initials: AK
authors.lastname: Tanswell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley
chemical_list: C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D052246:Cyclooxygenase 2 Inhibitors; D005663:Furans; D015232:Dinoprostone; D010100:Oxygen
keywords: PGE2; alveolar formation; bronchopulmonary dysplasia; chronic neonatal lung injury