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 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.
Chessex
P
P
Research Center, Hôpital Ste-Justine, Department of Pediatrics, University of Montreal, Quebec, Canada.
Lavoie
J C
JC
Laborie
S
S
Vallée
J
J
D000818:Animals; D005947:Glucose / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology; D018529:Nutritional Support; D010100:Oxygen / Q000378:metabolism; D013379:Substrate Specificity
D005978:Glutathione; D005947:Glucose; D010100:Oxygen