Genetic mutation in some Eastern Asians associated with aldehyde storm and an increased risk of liver disease

Scientists have identified a mechanism with which a joint genetic mutation increases the risk of liver disease. Their findings suggest that healthy choices, such as increasing antioxidants and limiting exposure to smoke, can reduce the risk of this disease.

Dehydrogenase 2 (Aldh2) is an important enzyme that detoxifies the harmful aldehydes produced in the body. Although it is best known for metabolizing aldehyde aldehyde increased by drinking – it also plays a role in the detoxification of other harmful aldehydes, including acrolein. Akrolein is a highly reactive aldehyde produced by exposing the environment to pollution, such as cigarette smoke. It damages proteins, DNA and lipids, contributing to cardiovascular disease, neurodegeneration and other states.

Some Eastern Asians have Genetic mutation () This impairs the ALDH2 function. It is estimated that about 40% of Japanese carry this mutation. Morticular carriers have an increased risk of esophageal cancer, especially among drinkers and smokers.

To understand how acute liver damage occurs in living organisms, when the detoxification of aldehyde is handicapped, the research group led by Professor Takeshi Izawa and the graduate Yuki also from the Graduate School of Veterinary Science, Osaka Metropolitan University, used Knock-in mice. These mice are bred to recreate the dysfunction of the ALDH2 enzyme observed in human media, which makes them useful for modeling processes leading to liver disease in humans and research of changes that occur when aldehydes are quickly produced in the body.

Scientists used allilic alcohol, alcohol that is metabolized in akrolein in the liver. They discovered that the elevated level of acrolein coincided with the level of many aldehydes growing in the blood, which they called “a storm of aldehyde”. This then causes the accumulation of aldehydes in the liver, causing serious damage to the liver. Their mechanism suggests damage that can be caused in people after exposure to a high level of acrolein, especially in people with gene variant.

The level of acrolein exposure used in this study clearly exceeds the level of smoking; Therefore, the risk of serious liver damage, such as reported in this article, is low by smoking is low. Instead, it is likely that the risk is higher in patients receiving anti -cancer drugs, such as cyclophosphamide, which is metabolized for acrolein in the body. “

Takeshi Izawa, associate professor, Osaka Metropolitan University

Usually acrolein is detoxified by antioxidant glutathione; However, this did not happen in mice. Instead, scientists have found that the levels of glutathione in the liver were seriously exhausted, which indicates the opposite relationship with the storm of aldehyde. Glutathione also suppresses oxidative stress, and therefore found that the impoverishment of glutathione was conducive to oxidative stress in the liver, leading to ferroptose, a type of cell death. Scientists found evidence of tissue damage in various organs, with the most severe liver.

“For the first time we identified a close relationship between aldehyde metabolism, the balance of redox and the Ferroptose trail,” he said Takami.

Their findings can also be important for people who carry a gene variant. These people usually have a reduced ability to break down alcohol aldehydes, some foods and environmental chemicals. In these people, the defense of the liver antioxidant can be overwhelmed by a sudden increase in aldehyde level, which leads to cell death and more serious liver damage. Their findings suggest that aldehyde storm is a key part of this process. It also emphasizes the importance of people with this variant, avoiding high exposure to aldehyde, supporting their antioxidant system through a healthy diet and monitoring liver health.

“Akrolein also occurs in electronic cigarette smoke and as a metabolite of anti -cancer drugs. The results of this study suggest that carriers may be threatened with health with daily exposure to aldehydes caused by smoking and some drugs,” said Izawa. “Going further, we plan to explore other effects on chronic exposure to health at aldehydes in media, in particular their involvement in cancer.”

The study was published in.