Pulmonary Antioxidant Enzyme Maturation in the Fetal and Neonatal Rat. I. Developmental Profiles

Abstract

SummaryNeonatal, adult, and fetal rat lungs of 18,20, and 22 d gestation from four to six litters were examined for cytochrome oxidase, glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, copper-zinc and manganese superoxide dismutase activities. All results were corrected for the contribution of enzymes in blood that contaminate homogenates. Because lung protein/ DNA ratios and body water change significantly with gestational age, enzyme activities were expressed as U/mg DNA. All activities were low in d 18 lung and increased with advancing gestational age. Only catalase and copper-zinc superoxide dismutase increased activity in response to air breathing, suggesting that maturation of the antioxidant enzyme system is virtually complete before delivery. Activities of glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, and manganese superoxide dismutase were higher in neonatal than in adult lung. AbbreviationsBPD, bronchopulmonary dysplasia CAT, catalase CYT OX, cytochrome oxidase G-6-PD, glucose-6-phosphate dehydrogenase GPX, glutathione peroxidase HBSS, Hank's balanced salt solution SOD, superoxide dismutase Premature delivery and exposure to elevated concentrations of inspired oxygen may be significant risk factors (8,14) for the development of BPD. Successful adaptation to a hyperoxic environment by young or adult animals of a number of species is associated with increased intrapulmonary concentrations of enzymes with antioxidant protective functions (6, 22).There is evidence that the initial cell damage observed in hyperoxic tissue occurs as a consequence of increased production of intracellular oxygen radicals by cell constituents, including mitochondria and endoplasmic reticulum (1 I , 20, 29). Cell survival requires the cell either to have adequate antioxidant defense mechanisms or to rapidly respond to oxidant stress by an increases of such mechanisms that can detoxify reduced species of oxygen and by-products. Because production of superoxide and hydrogen peroxide increases in lung cells as a function of oxygen concentration (1 1, 20, 29), the 5-fold increase in arterial oxygen tension which occurs after delivery (23) would be expected to pose significant oxidant stress to the normal neonatal lung, especially since an acute 5-fold increase in inspiratory oxygen concentration is lethal to adults of most species (20). The normal term newborn human infant, however, shows no clinical evidence of pulmonary oxidant damage, suggesting that adequate antioxidant defences have been induced in the lung before delivery. Gestation-dependent increases in antioxidant enzyme activities have been reported for placenta (30) and for catalase, but not GPX or SOD (18, 34) in liver. In rat brain GPX activity is similar, at birth, to that observed in adults whereas SOD activities are low compared with the adult (19).Postnatal changes in pulmonary antioxidant enzyme activities have been comprehensively documented (5, 15, 33) whereas, to our knowledge, antenatal changes have only been studied i...

The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

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Pentoxifylline and prevention of hyperoxia-induced lung ­injury in neonatal rats

“…However, preterm experimental animals and presumably newborn infants as well have deficient endogenous AOE activity and limited capacity to augment their levels of protective AOEs during oxygen exposure to overcome oxidative stress (7,8). Studies have established positive correlations between relative resistance to hyperoxia and increase of some or all of the pulmonary AOEs in newborn animals and humans (22,23). Bucher et al demonstrated a significant increase in GPX and SOD but not in CAT activity in newborn rats exposed to O 2 >95% for 6 d and in all three AOEs when exposed for 12 d (2).…”

Positive and negative regulatory elements in the upstream region of the rat Cu/Zn-superoxide dismutase gene

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