CHRONIC ETHANOL INGESTION IMPAIRS ALVEOLAR TYPE-II CELL GLUTATHIONE HOMEOSTASIS AND FUNCTION AND PREDISPOSES TO ENDOTOXIN-MEDIATED ACUTE EDEMATOUS LUNG INJURY IN RATS
F. Holguin et al., CHRONIC ETHANOL INGESTION IMPAIRS ALVEOLAR TYPE-II CELL GLUTATHIONE HOMEOSTASIS AND FUNCTION AND PREDISPOSES TO ENDOTOXIN-MEDIATED ACUTE EDEMATOUS LUNG INJURY IN RATS, The Journal of clinical investigation, 101(4), 1998, pp. 761-768
Chronic alcohol abuse increases the incidence and mortality of the acu
te respiratory distress syndrome (ARDS) in septic patients. To examine
a potential mechanism, we hypothesized that ethanol ingestion predisp
oses to sepsis-mediated acute lung injury by decreasing alveolar type
II cell glutathione homeostasis and function. Lungs isolated from rats
fed ethanol(20% in water for greater than or equal to 3 wk), compared
with lungs from control-fed rats, had greater (P < 0.05) edematous in
jury (reflected by nonhydrostatic weight gain) after endotoxin (2 mg/k
g intraperitoneally) and subsequent perfusion ex vivo with n-formylmet
hionylleucylphenylalanine (fMLP, 10(-7) M). Ethanol ingestion decrease
d (P < 0.05) glutathione levels in the plasma, lung tissue, and lung l
avage fluid, and increased (P < 0.05) oxidized glutathione levels in t
he lung lavage fluid, Furthermore, ethanol ingestion decreased type II
cell glutathione content by 95% (P < 0.05), decreased (P ( 0.05) type
II cell surfactant synthesis and secretion, and decreased (P < 0.05)
type II cell viability, in vitro, Finally, treatment with the glutathi
one precursors S-adenosyl-L-methionine and N-acetylcysteine in the fin
al week of ethanol ingestion significantly reduced lung edema during p
erfusion ex vivo, We conclude that ethanol ingestion in rats alters al
veolar type II cell glutathione levels and function, thereby predispos
ing the lung to acute edematous injury after endotoxemia, We speculate
that chronic alcohol abuse in humans predisposes to ARDS through simi
lar mechanisms.