Effects of chronic hepatic dysfunction on pulmonary glutathione homeostasis.
BACKGROUND
The development of acute respiratory distress syndrome (ARDS) in patients with pre-existing cirrhosis of the liver is associated with very high mortality. One possible cause may be alteration of pulmonary antioxidant capacity as a result of chronic hepatic dysfunction. Glutathione (GSH) is the most substantial nonprotein thiol in living organisms and likely plays a key role in neutralizing the oxidants and reactive oxygen species that are increased in ARDS. The lung is unable to synthesize GSH and is dependent on the liver. During periods of oxidant stress, individuals may exhibit relative deficiencies of GSH. With cirrhosis, the end result of chronic alcohol ingestion, this deficiency is more profound.


METHODS
Sixteen stable subjects with cirrhosis primarily due to alcohol consumption and 15 healthy controls underwent bronchoscopy and bronchoalveolar lavage with concurrent measurement of GSH in the plasma and the alveolar epithelial lining fluid (ELF).


RESULTS
For standardizing for saline dilution of the epithelial lining fluid as a result of bronchoalveolar lavage, GSH values are expressed in relation to immunoglobulin A (IgA). GSH in the ELF was profoundly reduced in the cirrhotic group [12.5 microg of GSH per microg of IgA (5.3-16.9 microg)] compared with the control group [64.0 microg of GSH per microg of IgA (55.1-242.5 microg); < 0.001]. The ratio of oxidized GSH to total GSH in the ELF was also significantly increased in the cirrhotic group [9.2% (5.1-16.4%) vs. 3.4% (1.7-5.7%); p < 0.003].


CONCLUSIONS
Despite a total reduction in GSH concentrations in the alveolar epithelial lining fluid of individuals with cirrhosis, the amount of oxidized GSH is increased. There is increased utilization of GSH despite the low supply in stable individuals with cirrhosis during steady state. These perturbations in GSH homeostasis in the alveolar epithelial lining fluid may be a factor in the poor outcomes seen in these individuals with ARDS.
Foreman
Marilyn G
MG
Department of Medicine, Division of Pulmonary and Critical Care, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. foremam@msm.edu
Hoor
Terri Ten
TT
Brown
Lou Ann S
LA
Moss
Marc
M
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric
D005978:Glutathione