Effect of dexamethasone and oxygen exposure on neonatal rat lung retinoic acid receptor proteins

Publisher Website
Google Scholar
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 μg/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/μg protein ± SEM) in both room air and oxygen groups: Air (11.2 ± 1.0) vs. Air/DEX (4.6 ± 1.3, n = 6; P 2, (18.2 ± 0.6) vs. O2/DEX (3.2 ± 0.6, n = 6; P 2- vs. air-exposed pups (18.2 ± 0.6, n = 6 vs. 11.2 ± 1.0, n = 5, P 2/DEX vs. O2 exposed groups, the decrease did not reach significance. However, the combination of O2/DEX significantly decreased CRABP binding (O2DEX, 30 ± 13, n = 3) when compared with air (109 ± 13, n = 5) and air/saline (133 ± 13, n = 6) (P 2-exposed neonatal pup lungs (55 ± 10, n = 4) than those exposed to air (109 ± 13, n = 5) This is the first report of DEX decreasing RP stores in neonatal rat lung and liver. We speculate that in sick premature infants receiving DEX, retinoids are mobilized from storage tissues to be utilized by tissue in need, such as during injury repair. This work also demonstrates a new possible interaction mechanism between DEX and retinoids at the functional level of RA binding proteins; DEX lowered RAR and CRABP binding activity.Pediatr Pulmonol. 1994;18:232–238. ©1994 Wiley-Liss, Inc.