Lowered glutathione levels can be as deadly to the lungs of alcohol abusers as alcohol itself can be to their livers and other organs, says David Guidot, M.D., associate professor of medicine at Emory University School of Medicine. Dr. Guidot will explain how glutathione depletion affects the lungs at a symposium on the cellular effects of chronic alcohol abuse at the Experimental Biology '02 meeting in New Orleans on April 24.
Until six years ago, when Emory scientist Marc Moss, M.D., first identified the connection between alcohol abuse and lung damage, scientists had not associated the two, even though alcohol's ill effects on the liver, brain and other organs was well recognized, according to Dr. Guidot, "We now know that as many deaths occur every year from alcohol abuse related to lung injury as occur from alcohol abuse and liver disease or alcohol abuse and traffic accidents," he notes. Scientists previously had not focused on the connection between alcohol and lung disease because the cause-and-effect relationship is indirect, unlike the direct effect of alcohol on the liver, explains Dr. Guidot. Dr. Guidot began studying the effects of glutathione depletion on the lungs while reviewing the mechanisms of alcohol toxicity in other organs. The body manufactures glutathione - a strong anti-oxidant molecule - from amino acids, which are the building blocks of proteins. Individuals with reasonably good diets maintain an adequate supply of glutathione, which is constantly being used up and replenished.
Although glutathione is manufactured in a variety of organs and tissues, including the liver, the lungs are particularly dependent on glutathione for protection from oxidative damage, especially in the small airways where breathing takes place. The lack of glutathione in the lungs leads to a variety of abnormalities, says Dr. Guidot, including damage to the epithelial cells and fluid that lines the lungs, changes in the barrier function of lung cells and increased susceptibility to apoptosis, or cell death in the lungs.
These abnormal cell changes in the lung caused by chronic alcohol abuse leave the lung vulnerable to injury when a serious illness such as sepsis or pneumonia occurs. "Heavy drinking and its relationship to lung disease is like driving on the highway without a seat belt," says Dr. Guidot. "It's risky behavior, but it doesn't cause injury unless you get in an accident. Alcohol doesn't cause lung disease unless you get sick, then the lungs are less able to respond to the challenges of infection."
The cure for alcohol-induced lung damage is not as simple as just taking extra doses of glutathione, Dr. Guidot points out, because an acute lung infection often is the first sign of damage. "If your house is on fire, it's too late to install a smoke detector," he says. Glutathione depletion cannot be quickly reversed. Only after the immediate illness is addressed can physicians consider treating a patient for alcoholism and consider long-term glutathione therapy.
By studying the mechanisms of glutathione damage, Dr. Guidot and his colleagues hope to design more effective therapies for preventing and treating the effects of chronic alcohol abuse.
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