Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress
Open accessAbstract
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 (5 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., β-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.
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Excessive alcohol intake is known to cause leaky gut with increased intestinal cell permeability and endotoxemia, possibly via increased CYP2E1 and oxidative stress.
“Excessive alcohol intake is known to cause leaky gut with increased intestinal cell permeability and endotoxemia, possibly via increased CYP2E1 and oxidative stress245–248.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [247]
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- Authors
- Cho, Y.-E., & Song, B.-J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Song, Byoung-Joon
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 18
- Pages
- 266-278
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC6080577
- OpenAlex
- W2884807256
- Cited by
- 78
- References
- 80
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 11 · 2023: 13 · 2022: 13 · 2021: 10 · 2020: 11 · 2019: 5 · 2018: 1
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-01-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Korea Research Institute of Bioscience and Biotechnology
- National Institute on Alcohol Abuse and Alcoholism
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Punica granatum, binge drinking, alcoholic liver disease, leaky gut, endotoxemia, oxidative stress, nitrative stress, intestinal tight junctions, adherens junctions, CYP2E1, inducible nitric oxide synthase, nitrated proteins, liver inflammation, intestinal barrier dysfunction
- MeSH terms
- Animals, Antioxidants, Female, Inflammation, Intestinal Mucosa, Intestines, Liver Diseases, Alcoholic, Nitrates, Permeability, Rats, Inbred F344, Apoptosis, Oxidative Stress, Tight Junctions, Plant Preparations, Lythraceae, Binge Drinking
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