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Effects of parenteral cysteine and glutathione feeding in a baboon model of severe prematurity^1,2,3

¹ From the Departments of Medicine and Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver; the University of Texas Health Sciences Center, Southwest Foundation for Biomedical Research, San Antonio, TX; and the National Jewish Medical and Research Center, Denver.

ABSTRACT

Background: The availability of cysteine for glutathione synthesis is low in premature infants with respiratory distress.

Objective: The effects of gestational age, oxygen delivery, and cysteine infusion or glutathione infusion, or both, on plasma total cysteine and other methionine metabolites were studied in a baboon model of severe premature birth with respiratory distress.

Design: Premature baboons were studied as part of the multiinvestigator National Institutes of Health Collaborative Project on Bronchopulmonary Dysplasia. Premature baboons, 125 d (69% of term) or 140 d (78% of term) of gestational age, were maintained in neonatal intensive care units for 14 d. Parenteral feeding with or without supplemental cysteine and glutathione infusions was given. Plasma total cysteine, methionine, N-methylglycine, cystathionine, and the other methionine metabolites were monitored by capillary gas chromatography–mass spectrometry.

Results: Cord blood plasma total cysteine was the lowest in the 125-d-old premature baboons. Plasma total cysteine decreased in the first 3 d after delivery in the 125-d-old (but not in the 140-d-old) premature baboons even when cysteine was infused. Supplementation with glutathione from the first day of life raised plasma total cysteine markedly. Plasma cystathionine increased in all animals after birth but increased 4-fold in 125-d-old animals with glutathione infusion. At 6 and 10 d postdelivery, the arterial-alveolar oxygen gradient was significantly higher in the 125-d-old animals that received glutathione infusions.

Conclusions: Glutathione, but not supplemental cysteine, infusions prevented the postdelivery decline in plasma cysteine concentrations in premature baboons. Glutathione infusions resulted in marked elevations of plasma cystathionine concentration.

Key Words: Baboons • prematurity • glutathione therapy • cystathionine • cysteine • N-methylglycine

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