Extracellular glutathione inhibits oxygen-induced permeability changes in alveolar epithelial monolayers.
Roum, J. H., A. S. Aledia, L. A. Carungcong, K.-J. Kim, and Z. Borok.
1Department of Medicine, University of California Irvine Medical Center, Orange 92868; and 2Will Rogers Institute Pulmonary Research Center and Departments of 3Medicine, 4Physiology and Biophysics, 5Biomedical Engineering, and 6Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California 90033
APStracts 8:0279A, 2001.
Exposure to high fractional inspired oxygen for 24 h increases permeability of the alveolar epithelium, contributing to the clinical manifestations of oxygen toxicity. Utilizing a model of the alveolar epithelium in which isolated rat type II cells form polarized monolayers on polycarbonate filters [transepithelial resistance (Rt) > 1 kO•cm2 by day 4], we evaluated the ability of reduced glutathione (GSH) to ameliorate these changes. On day 4, apical fluid was replaced with culture medium containing 1) no additives, 2) GSH (500 µM), or 3) GSH (500 µM) + glutathione reductase (0.5 U/ml) + nicotinamide adenine dinucleotide phosphate (250 µM). Monolayers were exposed (for 24 h) to room air (control) or 95% O2, each containing 5% CO2. After 24 h of hyperoxia, Rt for condition 1 decreased by 45% compared with control (P < 0.001). In conditions 2 and 3, Rt did not decrease significantly (P = not significant). Hyperoxia-induced decreases in active ion transport were observed for conditions 1 and 2 (P < 0.05), but not for condition 3 (P = not significant). These findings indicate that extracellular GSH may protect the alveolar epithelium against hyperoxia-induced injury. Addition of glutathione reductase and nicotinamide adenine dinucleotide phosphate may further augment these protective effects of GSH.
Received 7 July 2000; accepted in final form 5 March 2001
APS Manuscript Number A673-0.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001