GLUTATHIONE METABOLISM IN NEWBORNS - EVIDENCE FOR GLUTATHIONE DEFICIENCY IN PLASMA, BRONCHOALVEOLAR LAVAGE FLUID, AND LYMPHOCYTES IN PREMATURES

Respiratory distress in premature newborns is associated with deficien cy of surfactant in the bronchoalveolar lining fluid; this may be infl uenced by a local deficiency of antioxidants. Severe L-buthionine-S,R- sulfoximine-induced depletion of glutathione (GSH, a major antioxidant ) in rodents is associated with lung type 2 cell lamellar body damage and decreased concentrations in lung and bronchoalveolar lavage fluid (BALF) of phosphatidyl choline (a major component of surfactant). At b irth, prematurely born newborns (30-34 weeks) had lower peripheral ven ous plasma GSH concentrations than term (>36 weeks) babies; these leve ls decreased further with increasing prematurity (<27 weeks, with resp iratory distress). On day 2, the peripheral venous plasma GSH concentr ations reached a nadir, and the lowest levels were found in the most p remature newborns. Lymphocyte GSH concentrations were lowest on day 2 and day 7, and in prematures (<27 weeks, with respiratory distress) re mained below adult lymphocyte GSH levels for at least 4 weeks. At birt h, prematures (<27 weeks, with respiratory distress) had a central pla sma arterio-venous (A-V) GSH gradient across the lung (an estimate of lung uptake of GSH) of 0.72 +/- 0.15 (mean +/- SD) mu mol/L; on day 2, the A-V gradient did not change significantly (0.49 +/- 0.09 mu mol/L ). At birth, these prematures had markedly decreased BALF GSH concentr ations (compared with adult levels), and they were not significantly c hanged during the first 4 weeks of life. These results suggest that GS H deficiency is present in prematures and that it increases with the d egree of prematurity. At birth, GSH deficiency will compromise the lun gs' defense against oxidative stress injury. Oxidative stress is likel y to increase if hyperoxic treatment is given for respiratory distress in these infants. (C) 1995 Wiley-Liss, Inc.