Related Experiment Videos
Effect of dexamethasone and oxygen exposure on neonatal rat lung retinoic acid receptor proteins
K R McMenamy1, M J Anderson, R D Zachman
1Department of Pediatrics, University of Wisconsin, Madison.
Insights
Dexamethasone (DEX) treatment significantly reduces vitamin A levels in neonatal rat lungs and livers. This steroid also impairs retinoic acid receptor binding, potentially impacting lung development in premature infants with bronchopulmonary dysplasia (BPD).
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Endocrinology
Background:
- Retinol deficiency in animal models mimics airway changes seen in human bronchopulmonary dysplasia (BPD).
- Dexamethasone (DEX), a corticosteroid used for BPD, may influence vitamin A metabolism.
- Understanding DEX's effect on retinoid status is crucial for BPD treatment.
Purpose of the Study:
- To investigate the impact of Dexamethasone (DEX) on neonatal rat lung retinoid levels.
- To assess DEX's effect on retinoic acid (RA) receptor binding in lung tissues.
- To examine these effects under both room air and hyperoxic conditions.
Main Methods:
- Neonatal rats received DEX or saline, or no injection, and were exposed to room air or >95% oxygen.
- Lung and liver tissues were analyzed for retinyl palmitate (RP) levels.
- Nuclear retinoic acid receptor (RAR) and cellular retinoic acid binding protein (CRABP) binding were measured.
Main Results:
- DEX significantly decreased liver retinyl palmitate (RP) by 33-55%.
- DEX reduced neonatal rat lung RP by over 60%.
- DEX significantly decreased lung RAR binding in both room air and oxygen-exposed groups.
Conclusions:
- Dexamethasone (DEX) disrupts vitamin A homeostasis in neonatal rat lungs and livers.
- DEX treatment impairs retinoic acid receptor binding in lung tissue.
- These findings suggest a potential mechanism by which DEX might affect lung development in conditions like BPD.
Abstract:
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)