Dataset Information

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake.

ABSTRACT: Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/day of 56% (v/v) ethanol), three intervention groups with lutein (12, 24 and 48 mg/kg/day) and a positive control group (DG). The results showed that liver index, ALT, AST and TG levels were increased, and SOD and GSH-Px levels were reduced in the Et group. Furthermore, alcohol intake over a long time increased the level of pro-inflammatory cytokines TNF-α and IL-1β, disrupted the intestinal barrier, and stimulated the release of LPS, causing further liver injury. In contrast, lutein interventions prevented alcohol-induced alterations in liver tissue, oxidative stress and inflammation. In addition, the protein expression of Claudin-1 and Occludin in ileal tissues was upregulated by lutein intervention. In conclusion, lutein can improve chronic alcoholic liver injury and intestinal barrier dysfunction in rats.

SUBMITTER: Zhao S

PROVIDER: S-EPMC10005241 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake.

Zhao Suli S Zhang Yebing Y Ding Haoyue H Hu Shouna S Wu Xiaoqing X Ma Aiguo A Ma Yan Y

Nutrients 20230228 5

Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/da ...[more]

PMID: 36904226

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Project description:Alcohol liver disease (ALD) is a major cause of liver-related mortality globally, yet there remains an unmet demand for approved ALD drugs. The pathogenesis of ALD involves perturbations to the intestinal barrier and subsequent translocation of bacterial endotoxin that, acting through toll-like receptor 4 (TLR4), promotes hepatic inflammation and progression of ALD. In the present study we investigated the ability of fenretinide (Fen) [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid with known anti-cancer and anti-inflammatory properties, to modulate intestinal permeability and clinical hallmarks of ALD in a mouse model of chronic ethanol (EtOH) exposure. Our results show that EtOH-treated mice had reductions in mRNA and protein expression of intestinal tight junction proteins, including claudin one and occludin, and increases in intestinal permeability and endotoxemia compared to pair-fed mice. Also, EtOH-treated mice had marked increases in hepatic steatosis, liver injury, and expression of pro-inflammatory mediators, including TNF-α, and TLR4-positive macrophages, Kupffer cells, and hepatocytes in the intestines and liver, respectively. In contrast, EtOH + Fen-treated mice were resistant to the effects of EtOH on promoting intestinal permeability and had higher intestinal protein levels of claudin one and occludin. Also, EtOH + Fen-treated mice had significantly lower plasma levels of endotoxin, and reductions in expression of TNF-α and TLR4 positive macrophages, Kupffer cells, and hepatocytes in the intestine and liver. Lastly, we found that EtOH + Fen-treated mice exhibited major reductions in hepatic triglycerides, steatosis, and liver injury compared to EtOH-treated mice. Our findings are the first to demonstrate that Fen possesses anti-ALD properties, potentially through modulation of the intestinal barrier function, endotoxemia, and TLR4-mediated inflammation. These data warrant further pre-clinical investigations of Fen as a potential anti-ALD drug.

Project description:Background & aimsAlcoholic liver disease (ALD) is characterized by gut dysbiosis and increased gut permeability. Hypoxia inducible factor 1α (HIF-1α) has been implicated in transcriptional regulation of intestinal barrier integrity and inflammation. We aimed to test the hypothesis that HIF-1α plays a critical role in gut microbiota homeostasis and the maintenance of intestinal barrier integrity in a mouse model of ALD.MethodsWild-type (WT) and intestinal epithelial-specific Hif1a knockout mice (IEhif1α-/-) were pair-fed modified Lieber-DeCarli liquid diet containing 5% (w/v) alcohol or isocaloric maltose dextrin for 24 days. Serum levels of alanine aminotransferase and endotoxin were determined. Fecal microbiota were assessed. Liver steatosis and injury, and intestinal barrier integrity were evaluated.ResultsAlcohol feeding increased serum levels of alanine aminotransferase and lipopolysaccharide, hepatic triglyceride concentration, and liver injury in the WT mice. These deleterious effects were exaggerated in IEhif1α-/- mice. Alcohol exposure resulted in greater reduction of the expression of intestinal epithelial tight junction proteins, claudin-1 and occludin, in IEhif1α-/- mice. In addition, cathelicidin-related antimicrobial peptide and intestinal trefoil factor were further decreased by alcohol in IEhif1α-/- mice. Metagenomic analysis showed increased gut dysbiosis and significantly decreased Firmicutes/Bacteroidetes ratio in IEhif1α-/- mice compared to the WT mice exposed to alcohol. An increased abundance of Akkermansia and a decreased level of Lactobacillus in IEhif1α-/- mice were also observed. Non-absorbable antibiotic treatment reversed the liver steatosis in both WT and IEhif1α-/- mice.ConclusionIntestinal HIF-1α is essential for the adaptative response to alcohol-induced changes in intestinal microbiota and barrier function associated with elevated endotoxemia and hepatic steatosis and injury.Lay summaryAlcohol consumption alters gut microbiota and multiple intestinal barrier protecting factors that are regulated by intestinal hypoxia-inducible factor 1α (HIF-1α). Absence of intestinal HIF-1α exacerbates gut leakiness leading to an increased translocation of bacteria and bacterial products to the liver, consequently causing alcoholic liver disease. Intestinal specific upregulation of HIF-1α could be developed as a novel approach for the treatment of alcoholic liver disease.

Dataset Information

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake.

Publications

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake.

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