scholarly journals Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1386
Author(s):  
Dong-ha Kim ◽  
Yejin Sim ◽  
Jin-hyeon Hwang ◽  
In-Sook Kwun ◽  
Jae-Hwan Lim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Ellagic Acid ◽  
High Dose ◽  
Leaky Gut ◽  
Barrier Dysfunction ◽  
Gut Dysbiosis ◽  
Premature Deaths ◽  
Nitrative Stress

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

scholarly journals Translational Approaches with Antioxidant Phytochemicals against Alcohol-Mediated Oxidative Stress, Gut Dysbiosis, Intestinal Barrier Dysfunction and Fatty Liver Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 384
Author(s):  
Jacob W. Ballway ◽  
Byoung-Joon Song
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Intestinal Barrier ◽  
Leaky Gut ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Gut Dysbiosis ◽  
Disease States

Emerging data demonstrate the important roles of altered gut microbiomes (dysbiosis) in many disease states in the peripheral tissues and the central nervous system. Gut dysbiosis with decreased ratios of Bacteroidetes/Firmicutes and other changes are reported to be caused by many disease states and various environmental factors, such as ethanol (e.g., alcohol drinking), Western-style high-fat diets, high fructose, etc. It is also caused by genetic factors, including genetic polymorphisms and epigenetic changes in different individuals. Gut dysbiosis, impaired intestinal barrier function, and elevated serum endotoxin levels can be observed in human patients and/or experimental rodent models exposed to these factors or with certain disease states. However, gut dysbiosis and leaky gut can be normalized through lifestyle alterations such as increased consumption of healthy diets with various fruits and vegetables containing many different kinds of antioxidant phytochemicals. In this review, we describe the mechanisms of gut dysbiosis, leaky gut, endotoxemia, and fatty liver disease with a specific focus on the alcohol-associated pathways. We also mention translational approaches by discussing the benefits of many antioxidant phytochemicals and/or their metabolites against alcohol-mediated oxidative stress, gut dysbiosis, intestinal barrier dysfunction, and fatty liver disease.

A polysaccharide of PFP-1 from Pleurotus geesteranus attenuates alcoholic liver diseases via Nrf2 and NF-κB signaling pathways

2021 ◽  
Author(s):  
Xinling Song ◽  
Wenxue Sun ◽  
Wenxin Cai ◽  
Le Jia ◽  
Jianjun Zhang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Signaling Pathways ◽  
Alcoholic Liver Disease ◽  
Fruiting Body ◽  
Liver Diseases ◽  
Alcoholic Liver Diseases

A polysaccharide named as PFP-1 was isolated from Pleurotus geesteranus fruiting body, and the potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were processed...

Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

2021 ◽  
Author(s):  
Chitra Jairaman ◽  
Sabine Matou-Nasri ◽  
Zeyad I Alehaideb ◽  
Syed Ali Mohamed Yacoob ◽  
Anuradha Venkataraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Histopathological Examination ◽  
Bark Extract ◽  
High Dose ◽  
Protective Effects ◽  
Rhizophora Mucronata ◽  
Ethanol Intoxication ◽  
Hepatoprotective Effects

Abstract The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

scholarly journals Gut dysbiosis protects against liver injury in autophagy deficient mice by FXR-FGF15 feedback signaling

2020 ◽  
Author(s):  
Shengmin Yan ◽  
Bilon Khambu ◽  
Xiaoyun Chen ◽  
Zheng Dong ◽  
Grace Guo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Growth Factor ◽  
Liver Injury ◽  
Fibroblast Growth Factor ◽  
Liver Diseases ◽  
Farnesoid X Receptor ◽  
List Type ◽  
Fibroblast Growth ◽  
Gut Dysbiosis ◽  
Deficient Mice

ABSTRACTObjectiveThe gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM and in turn the effect of gut dysbiosis on liver injury.DesignFecal microbiota from mice with liver-specific loss of autophagy-related gene 5 (Atg5), Atg5Δhep mice, were analyzed by 16S sequencing. Antibiotics (ABX) was used to modulate GM in mice. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice over-expressing FGF15 gene, or given a fibroblast growth factor receptor 4 (FGFR4) inhibitor.ResultsThe composition of GM was significantly changed with a notable increase of BA-metabolizing bacteria in Atg5Δhep mice, leading to a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs in the intestine, which markedly activated ileal FXR with an increased expression of FGF15. ABX or cholestyramine treatment exacerbated liver injury and ductular reaction, and decreased FGF15 expression, whereas modulating FGF15 signaling altered liver phenotypes in the autophagy-deficient mice.ConclusionGut dysbiosis can remedy liver injury in Atg5Δhep mice through the FXR-FGF15 signaling. Antibiotics use in the condition of liver injury may have unexpected adverse consequences via the gut-liver axis.SHORT SUMMARYWhat is already known about this subject?Gut microbiota (GM) can be altered during hepatic pathogenesis.GM are involved in bile acid (BA) metabolism.Autophagy deficiency in the liver disrupts BA homeostasis and causes cholestatic injury.What are the new findings?Deficiency of autophagy in the liver causes alteration of GM, which leads to a higher proportion of BA-metabolizing bacteria.GM contribute to the activation of ileal farnesoid X receptor (FXR) and a higher expression of fibroblast growth factor 15 (FGF15) in autophagy deficient condition in the liver, which is associated with decreased levels of conjugated BAs and increased levels of unconjugated BAs in the intestine.Manipulations that lead to GM alteration, intestinal BA signaling, or FGF15 signaling can all modulate the liver phenotype.BA and GM together can act as a sensor to liver injury to trigger FGF15-mediated protective mechanism.How might it impact on clinical practice in the foreseeable future?These findings indicate that gut dysbiosis in the scenario of liver disease can be beneficial, suggesting cautions should be exercised in the use of antibiotics during specific liver diseases.If antibiotics need to be used in patients with liver diseases it may be beneficial to enhance the FXR-FGF15 feedback signaling to retain the protective effect of GM.

scholarly journals Oxidation of fish oil exacerbates alcoholic liver disease by enhancing intestinal dysbiosis in mice

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ruibing Feng ◽  
Li-Juan Ma ◽  
Meng Wang ◽  
Conghui Liu ◽  
Rujie Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Fish Oil ◽  
Alcoholic Liver Disease ◽  
Alcohol Exposure ◽  
Sequencing Analysis ◽  
Hepatic Inflammation ◽  
Barrier Dysfunction ◽  
Intestinal Dysbiosis ◽  
Junction Protein

AbstractThe role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial. N-3 PUFA oxidation in animal feeding stuffs was rarely concerned, likely contributing to inconsistent outcomes. Here, we report the impacts of oxidized fish oil (OFO) on ALD in C57BL/6 mice. Alcohol exposure increased plasma aminotransferase levels and hepatic inflammation. These deleterious effects were ameliorated by unoxidized FO but exacerbated by OFO. Sequencing analysis showed the accentuated intestinal dysbiosis and the increased proportion of Proteobacteria in OFO-fed mice. Intestinal sterilization by antibiotics completely abolished OFO-aggravated liver injury. Additionally, alcohol exposure leads to the greater increase in plasma endotoxin and decrease in intestinal tight junction protein expressions in OFO-fed mice. Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin.

scholarly journals Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 −/− mouse model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
J. Behary ◽  
A. E. Raposo ◽  
N. M. L. Amorim ◽  
H. Zheng ◽  
L. Gong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Gut Microbiome ◽  
Temporal Evolution ◽  
Inflammatory Responses ◽  
Therapeutic Interventions ◽  
Liver Inflammation ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Gut Dysbiosis

Abstract Background Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 −/− mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. Results Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. Conclusion In Mdr2 −/− mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.

scholarly journals Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Wang ◽  
Yan Zhao ◽  
Zhecheng Wang ◽  
Ruimin Sun ◽  
Boyang Zou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Liver Disease ◽  
Liver Injury ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Ros ◽  
Peroxiredoxin 3

Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

scholarly journals Intestinal Barrier in Human Health and Disease

2021 ◽  
Vol 18 (23) ◽  
pp. 12836
Author(s):  
Natalia Di Tommaso ◽  
Antonio Gasbarrini ◽  
Francesca Romana Ponziani
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Leaky Gut ◽  
Barrier Dysfunction ◽  
Permeable Barrier ◽  
Gut Dysbiosis ◽  
Health And Disease ◽  
And Function ◽  
The Relationship

The intestinal mucosa provides a selective permeable barrier for nutrient absorption and protection from external factors. It consists of epithelial cells, immune cells and their secretions. The gut microbiota participates in regulating the integrity and function of the intestinal barrier in a homeostatic balance. Pathogens, xenobiotics and food can disrupt the intestinal barrier, promoting systemic inflammation and tissue damage. Genetic and immune factors predispose individuals to gut barrier dysfunction, and changes in the composition and function of the gut microbiota are central to this process. The progressive identification of these changes has led to the development of the concept of ‘leaky gut syndrome’ and ‘gut dysbiosis’, which underlie the relationship between intestinal barrier impairment, metabolic diseases and autoimmunity. Understanding the mechanisms underlying this process is an intriguing subject of research for the diagnosis and treatment of various intestinal and extraintestinal diseases.

scholarly journals Schisandrin B: A Double-Edged Sword in Nonalcoholic Fatty Liver Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Pou Kuan Leong ◽  
Kam Ming Ko
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Er Stress ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Chinese Herb ◽  
High Dose ◽  
Schisandrin B ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit ofSchisandra chinensis(a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytesin vitroand in rodent liversin vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

scholarly journals Protective Effects of Ellagic Acid Against Alcoholic Liver Disease in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Liang Zhao ◽  
Arshad Mehmood ◽  
Mohamed Mohamed Soliman ◽  
Asra Iftikhar ◽  
Maryam Iftikhar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Ellagic Acid ◽  
Antioxidant Activities ◽  
Density Lipoprotein ◽  
Dietary Therapy ◽  
Control Group ◽  
Protective Effects ◽  
Gut Microbiota Dysbiosis

Ellagic acid, a natural polyphenolic compound commonly present in vegetables, fruits, nuts, and other edible plants, exerts many pharmacological activities. The present project was designed to explore the hepatoprotective effect of ellagic acid against alcohol-induced liver disease (ALD) and the correlation among alcohol, oxidative stress, inflammation, and gut microbiota. Fifty percent (v/v) alcohol (10 mL/kg bw daily) was orally administrated for 4 weeks in mice along with ellagic acid (50 and 100 mg/kg bw). Alcohol administration significantly (p < 0.05) increased the activities of alanine aminotransferase and serum aspartate aminotransferase, levels of triglyceride, low density lipoprotein, free fatty acid, and total cholesterol, and decreased contents of the high-density lipoprotein in model group compared with the control group, which were further improved by ellagic acid (50 or 100 mg/kg bw). Furthermore, daily supplementation of ellagic acid alleviated hepatic antioxidant activities (glutathione peroxidase, catalase, malondialdehyde, superoxide dismutase, and glutathione), proinflammatory cytokines levels (IL-6, IL-1β, and TNF-α), genes expressions (Tlr4, Myd88, Cd14, Cox2, Nos2, and Nfκb1), and histopathological features in alcohol-induced liver injured mice. Additionally, results also revealed that ellagic acid supplementation improved alcohol-induced gut microbiota dysbiosis. In conclusion, ellagic acid mitigated oxidative stress, inflammatory response, steatosis, and gut microbiota dysbiosis in ALD mice. Our results suggested that ellagic acid could be applied as an ideal dietary therapy against ALD.

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