Montelukast does not protect against hyperoxia-induced inhibition of alveolarization in newborn rats.
Impaired lung development has been demonstrated in neonatal animals exposed to hyperoxia. High lung cys-leukotriene levels may be a contributing factor towards the increase in oxygen toxicity. We investigated the effect of cysteinyl-leukotriene inhibition using the receptor antagonist, montelukast (MK, Singulair), on hyperoxia-induced changes in lung parenchymal structure in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or 50% O(2) (moderate hyperoxia) from days 1-14 after birth, and were administered the cys-leukotriene receptor antagonist MK (1 mg/kg/day) or normal saline from days 4-14. Somatic growth and morphometric measurements were done on day 15. There was a significant increase in bronchoalveolar lavage fluid cysteinyl-leukotriene levels (+61.9%) when animals were exposed to hyperoxia. O(2) exposure significantly decreased the specific internal surface area by 13%. There was a nonsignificant 5.8% and 19.6% increase in mean chord length and mean alveolar diameter, respectively, as well as an 8.6% decrease in lung volume to body weight ratio. Inhibition of only one arm of the arachidonic-acid cascade by MK was not sufficient to prevent these oxygen-induced changes.
Pediatric Intensive Care and Pulmonology Unit, Hôpital Pellegrin-Enfants, Bordeaux, France.
Philippe
P
Jouvencel
Michael
M
Fayon
Marie-Luce
ML
Choukroun
Dominique
D
Carles
Danielle
D
Montaudon
Eric
E
Dumas
Hughes
H
Begueret
Roger
R
Marthan
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D003521:Cyclopropanes; D018496:Hyperoxia / Q000503:physiopathology*; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000254:growth & development*; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast