Effect of dexamethasone and oxygen exposure on neonatal rat lung retinoic acid receptor proteins.
Retinol deficiency in animal models results in histopathologic airway changes that appear similar to those found in human premature infants with bronchopulmonary dysplasia (BPD). Dexamethasone (DEX), a steroid now often used in the treatment of BPD, might potentially affect lung vitamin A homeostasis since it alters serum and liver retinoid stores in certain models. Our objective was to determine the effect of DEX on neonatal rat lung retinoid status and the binding of retinoic acid (RA) to cytosolic and nuclear receptor proteins. We examined this effect both in room air and when the animals breathed 95% oxygen (O2). Twenty-four 1-day-old rat pups received either 1 microgram/g DEX subcutaneously, an equal volume of normal saline (NS) subcutaneously at 0 (start experiment time), 24, and 48 hours, or no injection at all, and were sacrificed at 72 hours. Twelve rats in each treatment group were housed in room air and 12 in each group were exposed to > 95% O2 for the 3 day period. Lung and liver were analyzed for retinyl palmitate (RP). Nuclear retinoic acid receptor (RAR) and cellular retinoic acid binding protein (CRABP) were measured by specific binding assays. DEX decreased liver RP by 33-55% and rat pup lung RP by over 60%; it also decreased lung RAR binding (mean dpm/microgram protein +/- SEM) in both room air and oxygen groups: Air (11.2 +/- 1.0) vs. Air/DEX (4.6 +/- 1.3, n = 6; P < 0.01), and O2 (18.2 +/- 0.6) vs. O2/DEX (3.2 +/- 0.6, n = 6; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of Wisconsin, Madison.
K R
KR
McMenamy
M J
MJ
Anderson
R D
RD
Zachman
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D004224:Diterpenes; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000187:drug effects* / Q000378:metabolism; D000084562:Retinyl Esters; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000378:metabolism
D004224:Diterpenes; D018168:Receptors, Retinoic Acid; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin; D003907:Dexamethasone; D010100:Oxygen