Research Teams at Mass General Explore Ways to Limit Alcohol-Induced Damage to the Liver and Better Understand Alcoholism’s Effect on the Brain

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Summer is almost upon us, which for many people means more outdoor time, cookouts, and for some—more drinking. While moderate alcohol consumption may have some health benefits, drinking too much can take a toll on our body. Researchers from Massachusetts General Hospital are investigating the long-term effects of excessive drinking on liver and brain function to find ways to reduce its impact on our health.

Enzyme treatment reduces alcohol-induced liver damage

Excessive drinking of alcohol can damage our liver in various ways. One way is through drinking more alcohol than the liver can process. And another is by making the gut’s intestinal membrane more permeable, which allows toxins to enter the blood stream and damage the liver.

Researchers in the lab of Richard Hodin, MD, in the Mass General Department of Surgery, reported in a new study that supplemental doses of an enzyme called intestinal alkaline phosphatase (IAP), which is known to stop bacterial toxins from entering the bloodstream through the gut, may also reduce liver damage from excess drinking.

In mouse models of binge drinking and chronic alcohol consumption, the research team found that feeding the mice a supplement of IAP reduced the amount of fat accumulation and inflammation in the liver and lessened signs of liver damage.

The enzyme appears to work in two ways. The first is by reducing the toxic effects of the lipopolysaccharide(LPS) molecule, which kills several important bacteria in the microbiome and can damage the liver if it passes through the intestinal membrane. The second is by reducing alcohol-induced membrane permeability in the intestine, which limits the overall amount of LPS that passes through the intestine. To be effective, the enzyme had to be administered before or at the same time as the alcohol. Administration after the fact had no effect. Human research is now being planned to confirm these results, and researchers plan to investigate other molecules that may have a role in liver inflammation.

“Liver damage is one of the most devastating effects of excess alcohol consumption, and so blocking this process could save millions of lives lost to alcohol-related liver diseases such as cirrhosis and liver cancer,” says Hodin, the study’s senior author. Read more here.

Imaging study reveals structural difference in brains of male and female alcoholics

It is known that alcoholic men and women have different psychological and behavioral profiles. Female alcoholics tend to have higher levels of anxiety, while male alcoholics tend to become more antisocial. But how do men and women’s brain structures that comprise the reward system that responds to alcohol compare? A collaborative study by researchers at Mass General and Boston University was the first to take a look.

The brain’s reward system includes the amygdala, which controls the fight or flight instinct, and the hippocampus, which controls long-term memory and emotional response.  The system is known to be involved in the development of substance abuse disorders like alcoholism.

In a study of 60 men and women with a history of alcoholism, along with a control group of non-alcoholics, researchers from the BU School of Medicine and the 3D Imaging Service and the Center for Morphometric Analysis in the Martinos Center for Biomedical Imaging at Mass General found that women with alcoholism tend to have a larger reward system than women without alcoholism—4.4 percent larger. It also confirmed previous studies that showed men with alcoholism tend to have smaller reward structures than those without—4.1 percent smaller.

It is not yet known if the differences in reward system size preceded the development of alcoholism or were a result of the disease. The results also suggest that alcohol works in different ways on the male and female brain, and that gender-specific approaches to treatment for alcoholism may be more effective than a one-size-fits-all approach. Learn more here.

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