Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress

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., 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.

Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells

“…These results agree with previous data reporting the antioxidant potential of punicalagin, an abundant ellagitannin present in pomegranate juice, that protects IEC-6 cells against heat stress-induced gastrointestinal injury by upregulating the expression of HO-1 via a mechanism that also involves Nrf2 translocation [56]. Moreover, pomegranate juice also increased tight junctions' proteins involved in the breakdown of the intestinal barrier during inflammatory response, such as Claudin-1 and ZO-1, a result consistent with previous evidence reporting the pomegranate's ability to prevent the changes in gut adherens junction proteins in binge alcohol-exposed rats [57].…”

Lactobacillus pentosus S-PT84 and Rubus suavissimus leaf extract suppress lipopolysaccharide-induced gut permeability and egg allergen uptake

“…These results were recognized in spite of using the healthy and young mouse that is housed in experimentally controlled environments. It has been reported that gut permeability is increased by alcohol intake (Schaffert et al 2009;Cho & Song 2018) and high fat diet (Singh et al 2017). Gut permeability is also increased in diabetes (Bosi et al 2006;Cani et al 2007).…”

“…It has been reported that various factors such as stresses, diet, dysbiosis, and drugs increase gut permeability (Ukena et al 2007;Zhang et al 2011;Singh et al 2017;Cho & Song 2018). There is a possibility that a significant increase in the intestinal permeability occurs without any subjective symptoms.…”

Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure

“…Synbiotic supplementation may also have exhibited these effects by decreasing oxidative stress induced by ethanol. Dietary supplementation with pomegranate [42] and symbiotic [14] suppressed oxidative stress in chronic-binge ethanol feeding in rats and mice, respectively. Oxidative stress has been implicated in the pathogenesis of various cardiovascular diseases [43], and the antioxidant properties of both butyrate and pomegranate may also be contributing to these effects in the liver.…”