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.
ABSTRACT
Prenatal alcohol exposure affects the cardiovascular health of the offspring. Epigallocatechin-3-gallate (EGCG) may be a protective agent against it, but no data are available regarding its impact on cardiac dysfunction. We investigated the presence of cardiac alterations in mice prenatally exposed to alcohol and the effect of postnatal EGCG treatment on cardiac function and related biochemical pathways. C57BL/6J pregnant mice received 1.5 g/kg/day (Mediterranean pattern), 4.5 g/kg/day (binge pattern) of ethanol, or maltodextrin until Day 19 of pregnancy. Post-delivery, treatment groups received EGCG-supplemented water. At post-natal Day 60, functional echocardiographies were performed. Heart biomarkers of apoptosis, oxidative stress, and cardiac damage were analyzed by Western blot. BNP and Hif1α increased and Nrf2 decreased in mice prenatally exposed to the Mediterranean alcohol pattern. Bcl-2 was downregulated in the binge PAE drinking pattern. Troponin I, glutathione peroxidase, and Bax increased in both ethanol exposure patterns. Prenatal alcohol exposure led to cardiac dysfunction in exposed mice, evidenced by a reduced ejection fraction, left ventricle posterior wall thickness at diastole, and Tei index. EGCG postnatal therapy restored the physiological levels of these biomarkers and improved cardiac dysfunction. These findings suggest that postnatal EGCG treatment attenuates the cardiac damage caused by prenatal alcohol exposure in the offspring.
ABSTRACT
Alcoholic liver disease (ALD) is a major chronic liver disease worldwide and can range from simple steatosis, inflammation to fibrosis/cirrhosis possibly through leaky gut and systemic endotoxemia. We investigated whether pomegranate (POM) protects against binge alcohol-induced gut leakiness, endotoxemia, and inflammatory liver damage. After POM pretreatment for 10 days, rats were exposed to 3 oral doses of binge alcohol (5â¯g/kg/dose) or dextrose (as control) at 12-h intervals. Binge alcohol exposure induced leaky gut with significantly elevated plasma endotoxin and inflammatory fatty liver by increasing the levels of oxidative and nitrative stress marker proteins such as ethanol-inducible CYP2E1, inducible nitric oxide synthase, and nitrated proteins in the small intestine and liver. POM pretreatment significantly reduced the alcohol-induced gut barrier dysfunction, plasma endotoxin and inflammatory liver disease by inhibiting the elevated oxidative and nitrative stress marker proteins. POM pretreatment significantly restored the levels of intestinal tight junction (TJ) proteins such as ZO-1, occludin, claudin-1, and claundin-3 markedly diminished after alcohol-exposure. In addition, the levels of gut adherent junction (AJ) proteins (e.g., ß-catenin and E-cadherin) and desmosome plakoglobin along with associated protein α-tubulin were clearly decreased in binge alcohol-exposed rats but restored to basal levels in POM-pretreated rats. Immunoprecipitation followed by immunoblot analyses revealed that intestinal claudin-1 protein was nitrated and ubiquitinated in alcohol-exposed rats, whereas these modifications were significantly blocked by POM pretreatment. These results showed for the first time that POM can prevent alcohol-induced gut leakiness and inflammatory liver injury by suppressing oxidative and nitrative stress.