Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Abstract

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 ≧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.

Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

“…In the murine model, Ohtsu et al (23) reported that higher doses of DXM (1 and 5 mg/kg/day) are required to affect survival and protect lung from hyperoxia in neonatal rats. We adopted an initial DXM dose of 0.5 mg/kg/day, because it was common initial dose used in the neonatal rat under hyperoxic conditions (24, 25). In published studies (7, 26), the postnatal HCS therapy in preterm infants, administered to prevent or treat BPD, consisted of a starting dose of 1-5 mg/kg/day.…”