Cyclooxygenase‐2 inhibition partially protects against 60% O2‐mediated lung injury in neonatal rats. Issue 10 (23rd November 2013)

• Record Type: Journal Article
• Authors: Masood, Azhar; Yi, Man; Lau, Mandy; Belcastro, Rosetta; Li, Jun; Kantores, Crystal; Pace‐Asciak, Cecil R.; Jankov, Robert P.; Tanswell, A. Keith
• Is Part Of: Pediatric pulmonology. Volume 49:Issue 10(2014:Oct.)
• Page Start: 991
• Page End: 1002
• Publication Date: 2013-11-23
• Subjects: Pediatric respiratory diseases -- Periodicals; Pediatrics -- Periodicals; 618.922
• DOI: 10.1002/ppul.22921
• Languages: English
• ISSNs: 8755-6863

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Summary</title> <sec id="ppul22921-sec-0001" sec-type="section"> <title>Rationale</title> <p>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.</p> </sec> <sec id="ppul22921-sec-0002" sec-type="section"> <title>Methods</title> <p>Neonatal rats exposed to air or 60% O<sub>2</sub> 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.</p> </sec> <sec id="ppul22921-sec-0003" sec-type="section"> <title>Results</title> <p>DFU attenuated the lung macrophage and neutrophil influx, prevented interstitial thickening and prevented the loss of peripheral blood vessels induced by 60% O<sub>2</sub>, but did not protect against the variance in alveolar diameter induced by 60% O<sub>2</sub>. Exposure to 60% O<sub>2</sub> caused both an increase in lung prostaglandin E<sub>2</sub> content and a reduction in lung mesenchymal cell mass which was reversed by DFU. Prostaglandin E<sub>2</sub> 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% O<sub>2</sub>.</p> </sec> <sec id="ppul22921-sec-0004" sec-type="section"> <title>Conclusions</title> <p>An highly selective cyclooxygenase‐2 inhibitor is an effective anti‐inflammatory substitute for dexamethasone for preventing phagocyte influx into the neonatal lung during 60% O<sub>2</sub>‐mediated lung injury, and can modify the severity of that injury. <bold>Pediatr Pulmonol. 2014; 49:991–1002.</bold> © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>