Domestic researchers unveiled a new mechanism by which reactive oxygen species (ROS) produced during alcohol consumption cause liver cell death and inflammatory responses.
Professor Jeong Won-il of the Korea Advanced Institute of Science and Technology (KAIST) and his research team, in collaboration with Professor Kim Won of Seoul National University Boramae Medical Center, noted on the 17th that they have identified the mechanisms of liver damage and inflammation (alcoholic steatohepatitis) caused by drinking at the molecular level. The research results were published in the international journal 'Nature Communications' on the 1st.
Excessive drinking leads to alcoholic liver disease, of which about 20% progresses to alcoholic steatohepatitis, which can result in cirrhosis and liver failure, making early diagnosis and treatment crucial.
The research team confirmed that during chronic drinking, the increased expression of 'vesicular glutamate transporter (VGLUT3)' leads to the accumulation of glutamate in liver cells, followed by a rapid change in intracellular calcium levels due to binge drinking, which induces glutamate secretion.
Glutamate is a type of amino acid, and when it is excessively present, it causes neurons to become hyperexcitable, leading to cell damage or death. The secreted glutamate stimulates the glutamate receptor (mGluR5) of Kupffer cells, the resident macrophages in the liver, inducing reactive oxygen species production, which subsequently leads to liver cell death and inflammatory responses.
Based on this, the research team demonstrated through animal models that genetically or pharmacologically inhibiting glutamate transporters, glutamate receptors, and reactive oxygen species-generating enzymes (NOX2) reduces alcohol-related liver damage.
Professor Jeong Won-il said, “This could serve as a new molecular target for diagnosis and treatment in the early stages of alcoholic steatohepatitis.”
References
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-60820-3