Effects of postnatal dexamethasone or hydrocortisone in a rat model of antenatal lipopolysaccharide and neonatal hyperoxia exposure

Abstract

The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O(2) groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O(2) + DXM and LPS + O(2) + HCS groups as compared to the LPS + O(2) alone group, and the LPS + O(2) + DXM group had thicker alveolar walls than the LPS + O(2) group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.

Keywords: Bronchopulmonary Dysplasia; Dexamethasone; Hydrocortisone; Lung Development.

Fig. 1

Schematic outline of the experimental protocol. LPS, lipopolysaccharide; L (0.75), lipopolysaccharide administered at 0.75 µg at gestation day 20; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone administered with a 6-day tapered course; HCS, hydrocortisone administered at a 6-day tapered course.

Fig. 2

Postnatal survival rates in the experimental groups. LPS, lipopolysaccharide; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone; HCS, hydrocortisone. ^*Significantly higher or lower than the control group.

Fig. 3

Postnatal weight gain in the experimental groups. Black, gray, and white bars indicate body weights on days 1, 7, and 14, respectively. Data are based on survival to day 14. LPS, lipopolysaccharide; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone; HCS, hydrocortisone. ^*Significantly higher or lower than the control group; ^†Significantly higher or lower than the LPS + O₂ group.

Fig. 4

Representative photomicrographs of rat lungs on day 14. H&E stained. Magnification × 100. Scale bars indicate 200 µm. LPS, lipopolysaccharide; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone; HCS, hydrocortisone.

Fig. 5

Morphometric data. Mean cord length (Lm) (A) and alveolar wall thickness (WT) (B). LPS, lipopolysaccharide; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone; HCS, hydrocortisone. ^*Significantly higher or lower than the control group; ^†Significantly higher or lower than the LPS + O₂ group; ^‡Significantly higher or lower than the LPS + O₂ + HCS group.

Fig. 6

Total cell count in bronchoalveolar lavage fluid (TCC in BALF) on D7 (open bars) and D14 (solid bars). LPS, lipopolysaccharide; O₂, exposure to 85% oxygen for 1 week; DXM, dexamethasone; HCS, hydrocortisone.