Nicotinamide Riboside Reduces Alcohol-Induced Inflammation and Oxidative Stress in Immune Cells: Preclinical Findings

Synopsis

Macrophages play an important role in inflammation and oxidative stress caused by alcohol. Researchers studied how nicotinamide riboside (NR), a precursor of NAD+, affects alcohol-induced inflammation and oxidative stress in macrophages. NR greatly reduced the expression of inflammatory genes caused by alcohol and also stopped a key inflammatory protein, NF-κB p65, from moving into the cell nucleus in two types of macrophages. When macrophages were exposed to alcohol or its breakdown product acetaldehyde, NR prevented the build-up of harmful reactive oxygen species. Alcohol lowered the levels and activity of SIRT1, a protein that protects cells, and decreased NAD+ levels, while increasing inflammatory gene activity. NR was able to reverse these effects. Blocking SIRT1 made alcohol-induced inflammation worse, while activating SIRT1 reduced it. Alcohol did not change the basic breakdown of glucose (glycolysis), but it increased the cell's ability to perform glycolysis and related activities, along with increasing HIF-1α, a protein that shifts cell metabolism toward lactate production. Alcohol also increased mitochondrial respiration and ATP production but lowered the maximum respiratory capacity and the number of mitochondria. NR stopped these alcohol-induced changes in both glycolysis and mitochondrial function in macrophages. Overall, NR shows anti-inflammatory and antioxidant effects by boosting SIRT1 and NAD+ levels, counteracting the negative impact of alcohol on these pathways. By restoring normal NAD+/NADH balance and activating SIRT1, NR helps prevent harmful changes in energy metabolism caused by alcohol in macrophages.

Journal

Laboratory Investigation