AJP - Lung Cellular and Molecular Physiology, Vol 257, Issue 6 411-L420, Copyright © 1989 by American Physiological Society
Oxygen tolerance in neonatal rats: role of subcellular superoxide generation
H. Ischiropoulos, C. E. Nadziejko, T. Kumae and Y. Kikkawa
Department of Pathology, College of Medicine, University of California, Irvine 92717.
We compared the superoxide anion generating capacity of subcellular
fractions from the lungs of neonatal and adult rats. Microsomal and
mitochondrial fractions from adult rats produced approximately three times
more superoxide (nanomoles per minute per milligram protein) than fractions
from neonatal rats in the presence of 100% O2. Subcellular superoxide anion
generating capacity was also examined in adult and neonatal rats exposed to
greater than 95% fractional concentration of O2 in inspired gas. The O2-
produced by mitochondrial and microsomal fractions of adult and neonatal
rats increased above control levels for the first 24 h and declined below
control values after 48 h of exposure in adults, whereas the elevated O2-
production was sustained in microsomal fractions of neonates through 60 h.
During the course of hyperoxic exposure, the largest difference in the
superoxide generating capacity between adult and neonate was observed after
8-24 h of hyperoxia. The microsomal and mitochondrial fractions from adult
rats produced three to seven times more O2- compared with neonatal rats.
Cu,Zn superoxide dismutase (SOD) increased during the course of hyperoxia
only in neonates at 8, 24, and 48 h of exposure. No change was observed in
the activity of Mn SOD. The ratio of SOD activity (units per lung) to
subcellular superoxide generating capacity (nanomoles per minute per lung)
was calculated for the normal adults and neonates. The ratio for adult rats
averaged 23 and 17 for mitochondrial and microsomal fractions,
respectively, and 51 for neonatal rats for both subcellular fractions under
normoxic conditions. These results suggest that O2- tolerance of neonates
may be explained by the favorable balance between antioxidant defenses and
subcellular superoxide generating capacity. The role of increased activity
of Cu,Zn SOD as an accompanying or a causative phenomenon in O2 tolerance
of neonates could not be determined from these experiments.
