Survival of guinea pig pups in hyperoxia is improved by enhanced nutritional substrate availability for glutathione production

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 anim al models. After the observation that newborn infants exposed to oxygen hav e low glutathione levels, a study was designed to test the hypothesis that in neonates from a species susceptible to oxygen toxicity, the lethal effec t of hyperoxia is related to a low availability of substrates for glutathio ne production rather than an impairment in synthetic activity. One-day-old guinea pigs, randomly assigned to room air or oxygen (>95%), were fed by th eir mothers (n = 16) or i.v. by dextrose (n = 14) or by total parenteral nu trition (TPN, n = 20). After 3 d, glutathione and activities of enzymes inv olved in maintaining intracellular glutathione levels were determined in lu ngs and liver. The lethal effect of oxygen (p < 0.05) observed in animals w ithout TPN was not related to glutathione depletion, as oxygen induced a 33 % increase in lung glutathione, positively correlated (r(2) = 0.35) with en hanced synthesis. With TPN, the animals were protected against the lethal e ffects of hyperoxia and lung glutathione increased by 67% in oxygen. The re sults suggest that the glutathione demand by the lungs in the presence of a n 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.