Baby Boomer Health and Wellness Center

Effects of Chronic Hepatic Dysfunction on Pulmonary Glutathione Homeostasis

Alcoholism: Clinical & Experimental Research. 26(12):1840-1845, December 2002.
Foreman, Marilyn G.; Hoor, Terri Ten; Brown, Lou Ann S.; Moss, Marc

Abstract:
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 [mu]g of GSH per [mu]g of IgA (5.3-16.9 [mu]g)] compared with the control group [64.0 [mu]g of GSH per [mu]g of IgA (55.1-242.5 [mu]g);p < 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.

2002 Research Society on Alcoholism

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What does this mean for those of us who are alcoholic or have alcoholic loved ones? Chronic alcoholism results in low levels of glutathione and in cirrhosis of the liver. Cirrhosis further depletes glutathione levels. Even though levels are down, there continues to be an increase in the amount of glutathione that the body uses (logically, this will further deplete supplies of the body’s primary antioxident). Disruptions in glutathione equilibrium in the alveolar epithelial lining fluid may be a factor in the poor outcomes seen in these individuals with ARDS.

Learn more about glutathione.

Have you ever heard of the metabolic syndrome in reference to cognitive impairment? Improving memory in later life may be as easy as avoiding Metabolic Syndrome. Metabolic syndrome is characterized by a group of metabolic risk factors in one person…this means that if you have three or more of five symptoms, you have the syndrome and a 66% higher risk of developing cognitive impairment than women who do not have syndrome. According to a large study done by the San Francisco VA Medical Center and the University of California and published in the March, 2009 issue of Archives of Neurology, the metabolic syndrome is defined by the presence of three or more of the following symptoms: abdominal obesity, elevated blood triglycerides (fatty acids), reduced HDL or ‘good’ cholesterol, elevated blood pressure, and Type 2 diabetes.

Interestingly enough, if each symptom is examined by itself, diabetes is the only one of the five symptoms that is normally associated with a higher risk of cognitive impairment. But, when more than one symptom is present, each additional symptom adds a 23% greater risk. This means that it is important for older folks with the metabolic syndrome to be screened early for cognitive impairment (and that the different symptoms of the syndrome should be treated early and aggressively, before a woman becomes post-menopausal).

The news is quite thought provoking, considering that 45% of American adults between the ages of 60 and 70 are believed to have metabolic syndrome. In fact, many 45-50 year old men and women are already exhibiting three of the five symptoms. The good news is that all five symptoms of metabolic syndrome are manageable, and most are even preventable or reversible. But more research is needed to determine whether managing or reversing symptoms will reduce the risk or if the damage has already been done. Once again, prevention is without a doubt much better than a cure.