The imbalance between high
oxidant loads and immature
antioxidant defenses is associated with long-term complications of prematurity.
Glutathione is a central
element among the
antioxidants. Depletion of pulmonary
glutathione accelerates the development of
oxygen-induced
lung injury in neonatal animal models. After the observation that newborn infants exposed to
oxygen have low
glutathione levels, a study was designed to test the hypothesis that in neonates from a species susceptible to
oxygen toxicity, the lethal effect of
hyperoxia is related to a low availability of substrates for
glutathione production rather than an impairment in synthetic activity. One-day-old guinea pigs, randomly assigned to room air or
oxygen (>95%), were fed by their mothers (n = 16) or i.v. by
dextrose (n = 14) or by
total parenteral nutrition (TPN, n = 20). After 3 d,
glutathione and activities of
enzymes involved in maintaining intracellular
glutathione levels were determined in lungs and liver. The lethal effect of
oxygen (p < 0.05) observed in animals without TPN was not related to
glutathione depletion, as
oxygen induced a 33% increase in lung
glutathione, positively correlated (r2 = 0.35) with enhanced synthesis. With TPN, the animals were protected against the lethal effects of
hyperoxia and lung
glutathione increased by 67% in
oxygen. The results suggest that the
glutathione demand by the lungs in the presence of an
oxidant stimulus was met by the increased (p < 0.001) hepatic production supported by TPN. Under hyperoxic conditions, early
nutritional support is of vital importance.