Depletion in Chronic Alcohol Abuse Makes Lungs Vulnerable to Life-Threatening
alcohol abuse causes a profound deficiency of the antioxidant glutathione
in the lungs, generating a marked susceptibility to serious lung diseases,
according to research at Emory University School of Medicine and the
Atlanta Veterans Affairs Medical Center.
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
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
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.