Effects of postnatal dexamethasone on oxygen toxicity in neonatal rats.
We investigated the effect of timing of early postnatal dexamethasone on survival of hyperoxia-exposed neonatal rats. Pups <24 h old were treated with a tapering course of dexamethasone or saline beginning either prior to exposure (day 0), or after 2, 4, or 6 days of > or =98% O2 (n=11-14) or air (n=8-11). Exposures were continued for 14 days. By day 14, day 0 pups had poor survival regardless of the exposure (14% in O2, 13% in air). Survival of pups treated with dexamethasone after 2, 4 and 6 days of O2 exposure was significantly higher at 14 days (50, 86 and 79%, respectively) compared to saline O2 controls (9%, p < 0.001 for each). Pulmonary biochemical analyses were conducted after exposure for 7 days in rat pups treated with dexamethasone or saline beginning after 4 days of exposure to air or O2 (n=11-12 for each group). While pups treated with dexamethasone showed greatly improved survival compared to O2 controls, there was no decrease in neutrophil influx into the lung as measured by lung myeloperoxidase and neutrophil counts in histologic specimens and lavage fluid. Catalase, glutathione peroxidase, total and manganese superoxide dismutase activities as well as manganese superoxide dismutase (MnSOD) mRNA expression were elevated in both O2 groups after 7 days compared to the air groups (p < 0.05) and MnSOD mRNA expression was elevated in the O2/dexamethasone group, but there were no differences between dexamethasone and saline groups in O2. Thus, this study indicates that the timing of dexamethasone administration is crucial. Mechanisms other than increases in antioxidant enzymes or decreases in lung neutrophils underlie the ability of dexamethasone to improve survival of these neonatal rats.
Dallas
Dara Varga
DV
Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555-0526, USA. ddallas@utmb.edu
Keeney
Susan E
SE
Mathews
Mary J
MJ
Schmalstieg
Frank C
FC
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D009504:Neutrophils; D010100:Oxygen / Q000008:administration & dosage / Q000633:toxicity*; D009195:Peroxidase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010100:Oxygen