New experiments with rodents suggest that, in terms of gene-expression changes, chronic drinking is more damaging to the liver than acute or binge drinking.
“Different patterns of drinking can produce a different set or pattern of gene expression by the liver because of adaptation by the liver which occurs when the same level of blood alcohol is repeated over and over again,” Samuel W. French, distinguished professor of pathology at the UCLA School of Medicine, was quoted in a press release announcing the findings.
“Unfortunately, these adaptive changes in gene expression are injurious to the liver and are furthermore persistent in the liver even when alcohol drinking has stopped. This is why people who develop liver disease after chronic alcohol abuse continue to be sick from liver damage for many months after they have stopped drinking. In fact, they actually get worse when they stop drinking because their liver is programmed epigenetically to work under the influence of alcohol. Think of it as deleterious conditioning and a learning process for the liver.”
French and his colleagues used microarray analysis on livers from rats that had been given an acute or binge dose of alcohol (the equivalent of 6 grams for every kilogram of body weight), enough to intoxicate the animals. The gene microarrays were then compared to those from an earlier study of rat livers that had been exposed to alcohol for one month (comprising 36 percent of their calories), the equivalent of chronic drinking.
Results showed that chronic exposure to alcohol leads to more gene-expression changes in the liver than acute exposure to alcohol does.
“The liver damage in the two groups was different,” said French. “For instance, after chronic abuse the liver cells become swollen and filled with fat stores, some liver cells died and cells in the liver that make scars are activated. These changes do not occur in the liver after an acute or binge dose, as demonstrated by gene expression.”
The important lesson in the rodent findings for humans, French added, is that daily, excessive drinking can “teach” the liver to become dependent on alcohol. Because of the genetic similarities between rodents and humans, the researchers believe their findings could lead to new treatments or research paths for human liver disease.
The results of the study will be published in the April issue of the journal Alcoholism: Clinical & Experimental Research.
