Increased lung antioxidant enzyme activity persists after a single
fetal dose of corticosteroids in preterm lambs.
Walther, Frans J., Remedios David-Cu, Elba I. Mehta, Daniel H. Polk,
Alan H. Jobe, Machiko Ikegami.
Department of Pediatrics, King-Drew Medical Center & UCLA, Los
Angeles, CA 90059, Perinal Laboratories, Harbor-UCLA Medical Center,
Torrance, CA 90502
APStracts 3:0043L, 1996.
While administration of exogenous corticosteroids accelerates the late
gestational rise in fetal rat and lamb lung antioxidant enzyme
activity, the effect of dosing intervals on these responses remains
uncertain. We studied the persistence and efficacy of the antioxidant
response in fetal lamb lung to a single fetal dose of corticosteroids
injected between 121 and 127 d gestational age. Fetal lambs received
0.5 mg/kg of betamethasone (n=35) or saline (n=26) by fetal
intramuscular injection 24 h, 48 h, 4 d, or 7 d prior to preterm
delivery at 128 d gestation (term=150 d). After delivery, the lambs
were ventilated for 40 min and killed. Total superoxide dismutase
(SOD), catalase, and glutathione peroxidase (GPX) activities (U/mg
DNA) and lipid hydroperoxide levels (nmol/mg DNA) were measured using
homogenized lung and standard methods. The saline injected controls
were similar at all time points with a mean + SD lung SOD activity of
96 + 14 U/mg DNA, catalase activity of 199 + 30 U/mg DNA, GPX
activity of 260 + 47 U/mg DNA, and lipid hydroperoxide level of 15.29
+ 4.44 nmol/mg DNA. Lung antioxidant enzyme activity was consistently
higher (p<0.001) and lipid hydroperoxide presence was lower
(p<0.005) in the betamethasone treated groups, which had a SOD,
catalase, and GPX activity of 155 + 27, 288 + 39, and 378 + 58 U/mg
DNA, respectively, and a lipid hydroperoxide level of 11.15 + 2.56
nmol/mg DNA. There were no differences between the betamethasone
treated groups, except for a trend (p=0.04) towards higher SOD
activity in the lambs with the shortest interval between treatment
and delivery. We conclude that the positive effect of a single fetal
dose of betamethasone on lung antioxidant enzyme activity occurs
within 24 h after exposure, persists over a period of 7 d without a
major change in the magnitude of the response, and leads to a
reduction in lipid hydroperoxide formation during immediate
postdelivery oxygen exposure.
Received 10 July 1995; accepted in final form 5 March 1996.
APS Manuscript Number L214-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96