Preparation for Birth into an O2-Rich Environment: the Antioxidant Enzymes in the Developing Rabbit Lung

Abstract

SummaryTo determine if some specific "preparation for birth" occurs in the developing lung to help assure its successful adaptation to a comparatively 02-rich world at birth, we measured the activities of the antioxidant enzymes in the developing lungs of rabbit fetuses from 10 d before parturition to several days after birth. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) activities showed similar maturational patterns with significant increases id activity, compared with earlier gestational levels, during the last 3-5 d before birth. During the final days in utero, SOD and CAT activities increased by -110% and lung GP activity by -200%. There were no parallel changes in lung Oz consumption demonstrable over this same prenatal period. High concentrations of 0 2 are toxic to the lungs of all species, including man. The principal biochemical defense against 02-induced lung damage is generally accepted to be the antioxidant enzymes-SOD, CAT, and the GP system-and the lipid membrane constituent, Vitamin E (8,15,17,41). Studies from our own and other laboratories have established positive correlations between relative resistance to hyperoxia and increased levels of some or all of the pulmonary antioxidant enzymes (4,8,(15)(16)(17)41). It was noted a few years ago that SOD, CAT, and GP activities were all higher in the lungs of newborn rats than in the lungs of 2-d premature rat fetuses (43). In another study, SOD activity in the lungs from a small sampling of premature infants (26-32 wk gestation) ( n = 3) was found to be substantially lower than the SOD activity in the lungs of full-term newborns (n = 4) (1). These findings, combined with the fact that at birth the newborn leaves a hypoxic uterine environment (fetal arterial Poz -20-25 mm Hg) (7, 29) to enter a relatively hyperoxic 21% Oz environment, have made us wonder if some specific "preparation for birth" occurs in the developing lung to help assure its successful adaptation to a comparatively 02-rich world at birth. To examine the question, we have measured the activities of the antioxidant enzymes in the developing lungs of rabbit fetuses at intervals from 10 d before parturition (gestation period = 31.5 d) to several days after birth. We report here the changes in these protective enzymes that occur over this extended developmental period. Abbreviations MATERIALS AND METHODSAnimals. Pregnant California-strain rabbits were obtained from K-W Farms, Tice, FL. The exact breeding times (2 1 h) were provided by the supplier.All the fetuses used were delivered on the same day by hysterotomy under ketamine:xylazine anesthesia (90 mg/kg: 10 mg/kg) (Ketalar, Parke-Davis, Moms Plains, NJ; Rompun, Payvet Division-Cutter Labs, Shawnee, KS). All the pups used were sacrificed by an overdose of sodium pentobarbital administered intraperitoneally. The timed-gestations were interrupted at 2 1, 22, 26, 28, and 30 d. The pups used were <1-h old, 3-4-d-old, and 5-6-d-old. Adult does used for lung enzyme studies were sacrificed by pentobarbital over...

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