title: Ethanol ingestion via glutathione depletion impairs alveolar epithelial barrier function in rats.
abstract: We determined that rats fed a liquid diet containing ethanol (36% of calories) for 6 wk had decreased (P < 0.05) net vectorial fluid transport and increased (P < 0.05) bidirectional protein permeability across the alveolar epithelium in vivo compared with rats fed a control diet. However, both groups increased (P < 0.05) fluid transport in response to epinephrine (10(-5) M) stimulation, indicating that transcellular sodium transport was intact. In parallel, type II cells isolated from ethanol-fed rats and cultured for 8 days formed a more permeable monolayer as reflected by increased (P < 0.05) leak of [(14)C]inulin. However, type II cells from ethanol-fed rats had more sodium-permeant channels in their apical membranes than type II cells isolated from control-fed rats, consistent with the preserved response to epinephrine in vivo. Finally, the alveolar epithelium of ethanol-fed rats supplemented with L-2-oxothiaxolidine-4-carboxylate (Procysteine), a glutathione precursor, had the same (P < 0.05) net vectorial fluid transport and bidirectional protein permeability in vivo and permeability to [(14)C]inulin in vitro as control-fed rats. We conclude that chronic ethanol ingestion via glutathione deficiency increases alveolar epithelial intercellular permeability and, despite preserved or even enhanced transcellular sodium transport, renders the alveolar epithelium susceptible to acute edematous injury.
authors.affiliation: Atlanta Veterans Affairs Medical Center, Decatur 30033, USA. dguidot@emory.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Guidot
authors.forename: K
authors.initials: K
authors.lastname: Modelska
authors.forename: M
authors.initials: M
authors.lastname: Lois
authors.forename: L
authors.initials: L
authors.lastname: Jain
authors.forename: I M
authors.initials: IM
authors.lastname: Moss
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: L A
authors.initials: LA
authors.lastname: Brown
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004338:Drug Combinations; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D005978:Glutathione / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D011355:Prodrugs / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
chemical_list: D002412:Cations; D004338:Drug Combinations; D007473:Ion Channels; D011355:Prodrugs; D013844:Thiazoles; D053778:Thiazolidines; D000431:Ethanol; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid