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 deficiency of surfactant in the bronchoalveolar lining fluid; this may be influenced 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 birth, prematurely born newborns (30-34 weeks) had lower peripheral venous plasma GSH concentrations than term (> 36 weeks) babies; these levels decreased further with increasing prematurity (< 27 weeks, with respiratory distress). On day 2, the peripheral venous plasma GSH concentrations reached a nadir, and the lowest levels were found in the most premature newborns. Lymphocyte GSH concentrations were lowest on day 2 and day 7, and in prematures (< 27 weeks, with respiratory distress) remained below adult lymphocyte GSH levels for at least 4 weeks. At birth, prematures (< 27 weeks, with respiratory distress) had a central plasma arterio-venous (A-V) GSH gradient across the lung (an estimate of lung uptake of GSH) of 0.72 +/- 0.15 (mean +/- SD) mumol/L; on day 2, the A-V gradient did not change significantly (0.49 +/- 0.09 mumol/L). At birth, these prematures had markedly decreased BALF GSH concentrations (compared with adult levels), and they were not significantly changed during the first 4 weeks of life. These results suggest that GSH deficiency is present in prematures and that it increases with the degree of prematurity. At birth, GSH deficiency will compromise the lungs' defense against oxidative stress injury. Oxidative stress is likely to increase if hyperoxic treatment is given for respiratory distress in these infants.
Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107-5244, USA.
A
A
Jain
T
T
Mehta
P A
PA
Auld
J
J
Rodrigues
R F
RF
Ward
M K
MK
Schwartz
J
J
Mårtensson
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005978:Glutathione / Q000032:analysis* / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008214:Lymphocytes / Q000737:chemistry*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism
D005978:Glutathione