Pomegranate-Derived Exosome-Like Nanovesicles Alleviate Binge Alcohol-Induced Leaky Gut and Liver Injury.

ABSTRACT

Alcoholic liver disease (ALD) is damage to the liver and mainly caused by binge alcohol. ALD have decreased junctional protein expression and modulated intestinal permeability. We investigated whether plant-releasing exosome-like nanovesicles can prevent liver damage and leaky gut from binge alcohol. In this study, we characterized the exosome-like nanovesicles from pomegranate juice and confirmed the round shape of a lipid bilayer. After 14 days of pomegranate-derived exosome-like nanovesicle (PNVs) pretreatment, binge alcohol (6 g/kg/dose) was administered to mice three times orally every 12 h. Exposure to binge alcohol increased levels of oxidative and nitric oxide stress marker proteins such as CYP2E1, 3-Nitrotyrosine, and inducible nitric oxide synthase in both liver and gut damage. Also, binge alcohol significantly elevated the plasma endotoxemia, inflammatory fatty liver, and leaky gut. However, PNVs reduced the oxidative stress and apoptosis marker proteins and prevented the leaky gut and endotoxemia. Markedly, PNV treatment significantly prevented a decrease in the amount of intestinal junctional proteins and an increase in leaky gut in mice exposed to alcohol. These results showed that PNVs can prevent leaky gut and liver damage caused by binge alcohol and suggest that it may be useful hepatoprotective or intestinal protective agents for the first time.