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Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress.
Cho, Young-Eun; Song, Byoung-Joon.
Affiliation
  • Cho YE; Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
  • Song BJ; Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA. Electronic address: bj.song@nih.gov.
Redox Biol ; 18: 266-278, 2018 09.
Article in En | MEDLINE | ID: mdl-30071471
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 (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., 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.
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Full text: 1 Database: MEDLINE Therapeutic Methods and Therapies TCIM: Terapias_biologicas / Plantas_medicinales Main subject: Lythraceae / Plant Preparations / Intestines / Liver Diseases, Alcoholic / Nitrates / Antioxidants Type of study: Etiology_studies Language: En Journal: Redox Biol Year: 2018 Type: Article Affiliation country: United States

Full text: 1 Database: MEDLINE Therapeutic Methods and Therapies TCIM: Terapias_biologicas / Plantas_medicinales Main subject: Lythraceae / Plant Preparations / Intestines / Liver Diseases, Alcoholic / Nitrates / Antioxidants Type of study: Etiology_studies Language: En Journal: Redox Biol Year: 2018 Type: Article Affiliation country: United States