The research, presented today at the annual meeting of the Research Society on Alcoholism in San Francisco, describes a chemical found in the urine of monkeys also found in human alcoholics, and liver biopsies that show development of "fatty liver" -- another common finding in heavily drinking people.
Carol C. Cunningham, Ph.D., professor of biochemistry said, "One of the unique features of using these monkeys as a model for alcoholic liver disease is that these monkeys self-administer alcohol."
Some of the monkeys choose to only take a small amount of alcohol -- paralleling the social drinkers; some consume a moderate amount -- "like regular drinkers who are not in jeopardy of developing alcoholic liver disease," and some are heavy drinkers, who become intoxicated, most prone to changes in the liver.
"In some respects, this group of monkeys mimic the human situation," he said, except "we don't have any monkeys that don't drink any (alcohol) -- they all drink something."
First, Cunningham and his colleagues in the Center for the Neurobehavioral Study of Alcohol found evidence in the urine of "oxidative damage" to the liver. He explained that the metabolism of alcohol in the liver generates "reactive oxygen" which can damage liver tissue. To track that, they chose to follow damage to lipids, since cell structure is influenced by lipids.
The damaged liver produces isoprostanes in the urine -- tiny pieces of oxidized lipids. "There is a dramatic increase in the level of these lipid products in heavy drinkers," Cunningham
said. There are some isoprostanes in the urine of moderately drinking monkeys and only low amounts in the light drinkers.
Second, biopsies of the livers of the heavily drinking monkeys found evidence of "fatty liver." He said, "That is very characteristic of what one sees in alcoholics."
This is still a reversible stage of alcoholic liver disease.
He said he has seen no evidence so far of cirrhosis of the liver. But in some more recent biopsies, Cunningham and his colleagues noted some evidence of increased collagen staining within the liver tissue, perhaps pointing to the development of collagen fibrosis. He said the researchers were continuing to take biopsies regularly to see if fibrosis or liver inflammation develop.
Cunningham said that one of his goals in the study was to develop diagnostic procedures that are similar to those used in the clinic for humans. "Can we follow the progression of this disease in monkeys by looking at blood samples, urine samples and needle biopsies?"
"The animal model may be very useful in understanding alcoholism," said Cunningham. "We've worked out some procedures that allow us to analyze during the periods they are on the ethanol (alcohol.) We can carry out these studies indefinitely."
Contact: Robert Conn (rconn@wfubmc.edu), Jim Steele (jsteele@wfubmc.edu) or Mark Wright (mwright@wfubmc.edu) at (336) 716-4587.
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