The Effect of Hyperoxic Exposure on Antioxidant Enzyme Activities of Alveolar Type II Cells in Neonatal and Adult Rats

Abstract

ABSTRAfl. Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type I1 cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type I1 cells compared with adults. Baseline enzyme activities did not differ in neonatal type I1 cells and lung homogenates except for lower catalase activity in type I1 cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type I1 cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type I1 cells there was a significant decrease in SOD activity after 0 2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type I1 cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type I1 cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type 11 cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate. 4in cellular protective mechanisms, such as the antioxidant enzyme system, which includes the enzymes GPX, CAT, and SOD (5). It is known that the neonatal animal responds to exposure to >95% 0 2 with increased activities of antioxidant enzymes in the lung, an enzyme response not observed in the adult lung (2-4).The particular cell types that may be responsible for increases in antioxidant enzyme activity in the neonate have not been identified. Previous investigations of adult type I1 cells have produced conflicting data on whether antioxidant enzyme activities are higher in type I1 cells than in whole lung and whether antioxidant enzyme activities in type I1 cells increase after hyperoxia (6, 7). One previous investigation of neonatal type I1 cells has suggested that antioxidant enzyme activities do not increase in this cell type after hyperoxia (8). However, because the type I1 cell is relatively resistant to oxygen damage compared with other cell types and appears to be important for proliferation and repair of the pulmonary epithelial lining after damage (5, 9), we hypothesized that this cell might play a role in neonatal tolerance. This study was designed to test the hypotheses that 1) baseline (air-exposed) antioxidant enzyme activities would be higher in neonatal type I1 cells than in whole lung and 2) the activities of the antioxidant enzymes in neonatal type I1 cells would rise to a greater extent in...

Developmental differences in hyperoxia-induced oxidative stress and cellular responses in the murine lung

“…One mechanism to explain why our cellular responses contrast with the enhanced newborn tolerance to hyperoxia observed in vivo may relate to the newborn’s ability to augment antioxidant expression in response to oxidant stress as suggested in other models (17, 18, 21, 39, 40). To test this question we measured the induction of antioxidant enzymes during 24 hr hyperoxia.…”

Hyperoxia induces paracellular leak and alters claudin expression by neonatal alveolar epithelial cells

“…Interestingly, even brief exposures to 100% oxygen results in increased lung/wet dry ratio, bronchoalveolar protein concentrations, and perivascular edema in animals models of lung injury, and antioxidant deficiency exaggerates this effect, suggesting that oxidative balance is critical in the prevention of pulmonary edema . Neonatal animals have been shown to have a greater increase in antioxidant availability, particularly by AECs, in response to a hyperoxia challenge relative to adult animals . However, over time, when the neonatal protection against oxygen diminishes, antioxidant responses, such as Nrf‐2 activity and the availability of enzymes such as superoxide dismutase, glutathione reductase and catalase, may be impaired …”

“…35,36 Neonatal animals have been shown to have a greater increase in antioxidant availability, particularly by AECs, in response to a hyperoxia challenge relative to adult animals. 37,38 However, over time, when the neonatal protection against oxygen diminishes, antioxidant responses, such as Nrf-2 activity and the availability of enzymes such as superoxide dismutase, glutathione reductase and catalase, may be impaired. 35,[39][40][41] Limited information is available about the effects of hyperoxia on claudin localization and expression.…”

The Impact of Hyperoxia on the Neonatal and Adult Developing Dendritic Cell

“…Adult cells have been shown to have lesser amounts or activity of antioxidative enzymes (24,25). Adults also produce higher amounts of monocyte chemotactic protein-1 after hyperoxic exposure, which can amplify the production of inflammatory cytokines (26) that may result in cell death.…”