Premature rabbits, unlike full-term rabbits, are unable to mount a protective increase in pulmonary antioxidant enzyme (AOE) activities in response to 48 h of hyperoxic exposure and demonstrate increased pulmonary O2 toxicity compared with full-term rabbits. To examine AOE gene expression of CuZn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase in preterm versus term rabbits in response to hyperoxia, 29.5 d preterm rabbits (delivered by hysterotomy) and term rabbits (spontaneously vaginally delivered) were exposed to 48 h of >90% O2 or room air. Preterm rabbits had a significant increase in CuZn SOD mRNA without corresponding AOE activity increases, suggesting translational/posttranslational inhibition. In full-term rabbits, the magnitude of lung AOE mRNA changes was associated with concordant magnitude changes in activities of CuZn SOD, Mn SOD, and catalase, suggesting pretranslational regulation of AOE gene expression; glutathione peroxidase, however, appears to be regulated translationally/posttranslationally. To investigate potential pharmacologic means of overcoming the susceptibility of the preterm rabbit to O2 toxicity, 29.5 d preterm rabbits received 20-40 μg/kg of Salmonella typhimurium endotoxin or diluent S.C. (after birth and at 24 h); in separate experiments, pregnant rabbits received intramuscular injections of dexamethasone (0.01- 0.05 mg/kg) or saline on gestational d 27.5 and 28.5 and underwent hysterotomy at 29.5 d. After hyperoxic exposure, postnatal endotoxin treatment of preterm rabbits resulted in significant increases in CuZn SOD activity and CuZn SOD mRNA, suggesting a reversal of the translational/posttranslational inhibition characteristic of the preterm rabbit, improved hyperoxic survival (74/81 = 91% versus 70/92 = 76%, p < 0.05; endotoxin versus controls), and protection against hyperoxia-induced increases in lung lavage protein (+4% endotoxin versus +28% controls, p < 0.05). Prenatal dexamethasone neither improved hyperoxic survival, protected against O2 toxicity, nor produced increases in any of the AOE after 48 h of hyperoxia relative to air-breathing preterm rabbits.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health