scholarly journals Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 774
Author(s):  
Yoon Mee Yang ◽  
Ye Eun Cho ◽  
Seonghwan Hwang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Pathological Features ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
The Relationship

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

scholarly journals Hylocereus polyrhizus Peel Extract Retards Alcoholic Liver Disease Progression by Modulating Oxidative Stress and Inflammatory Responses in C57BL/6 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3884
Author(s):  
Wan-Ju Yeh ◽  
Chia-Chun Tsai ◽  
Jung Ko ◽  
Hsin-Yi Yang
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Protein Expression ◽  
Alcoholic Liver Disease ◽  
Inflammatory Responses ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Peel Extract ◽  
Hylocereus Polyrhizus

Alcoholic liver disease (ALD) has become a health problem as alcohol consumption has increased annually. Hepatic lipid accumulation, oxidative stress, and inflammation are important factors in the progression of ALD. Red pitaya (Hylocereus polyrhizus (Weber) Britt. & Rose) peel is rich in polyphenols and betanins, which possess antioxidative and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effects of red pitaya peel extract (PPE) on ALD and explore the associated mechanisms. C57BL/6 J mice were administered an ethanol liquid diet for 11 weeks with or without two different doses of PPE (500 and 1000 mg/kg BW). PPE treatment significantly ameliorated liver injury and hepatic fat accumulation, and it improved hepatic lipid metabolism via increases in AMPK and PPAR-α protein expression and a decrease in SREBP-1 expression. In addition, PPE inhibited CYP2E1 and Nrf2 protein expression, reduced endotoxin levels in the serum, and decreased TLR4 and MyD88 expression and inflammatory cytokine TNF-α and IL-1β levels in the liver. In conclusion, these findings suggest that PPE may prevent the progression of ALD by modulating lipid metabolism and reducing oxidative stress and inflammatory responses.

scholarly journals Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Aditya Ambade ◽  
Pranoti Mandrekar
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Proinflammatory Cytokine Production ◽  
The Past ◽  
Proinflammatory Responses ◽  
Progression Of Disease ◽  
Oxidative Processes

Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative stress and inflammation and highlight signaling intermediates regulated by oxidative stress that provokes proinflammatory responses in alcoholic liver disease.

scholarly journals Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Junyi Chu ◽  
Ran Yan ◽  
Sai Wang ◽  
Guoyang Li ◽  
Xiaohui Kang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Cell Damage ◽  
Sinapic Acid ◽  
Antioxidant Response ◽  
Docking Analysis ◽  
Molecule Docking ◽  
Acid Compound

Alcoholic liver disease (ALD) is one of the main causes of death in chronic liver disease. Oxidative stress and pyroptosis are important factors leading to ALD. Bromodomain-containing protein 4 (BRD4) is a factor that we have confirmed to regulate ALD. As a phenolic acid compound, sinapic acid (SA) has significant effects in antioxidant, anti-inflammatory and liver protection. In this study, we explored whether SA regulates oxidative stress and pyroptosis through BRD4 to play a protective effect in ALD. Male C57BL/6 mice and AML-12 cells were used for experiments. We found that SA treatment largely abolished the up-regulation of BRD4 and key proteins of the canonical pyroptosis signalling in the liver of mice fed with alcohol, while conversely enhanced the antioxidant response. Consistantly, both SA pretreatment and BRD4 knockdown inhibited oxidative stress, pyroptosis, and liver cell damage in vitro. More importantly, the expression levels of BRD4 and pyroptosis indicators increased significantly in ALD patients. Molecule docking analysis revealed a potent binding of SA with BRD4. In conclusion, this study demonstrates that SA reduces ALD through BRD4, which is a valuable lead compound that prevents the ALD process.

scholarly journals Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiwen Zhou ◽  
Meifei Wu ◽  
Lei Xu ◽  
Jieling Cheng ◽  
Jie Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Glycolytic Pathway ◽  
Tissue Samples ◽  
M1 Macrophage ◽  
Macrophage Phenotypes

Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. In vitro, blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What’s more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD.

scholarly journals A study of alanine aminotransferase - aspartate aminotransferase as a marker of advanced alcoholic liver disease

2020 ◽  
Vol 7 (4) ◽  
pp. 551
Author(s):  
Aravind G. N. ◽  
Abhilash K. ◽  
Syed Umar Farooq
Keyword(s):  
Liver Disease ◽  
Alcohol Consumption ◽  
Chronic Liver Disease ◽  
Alcoholic Liver Disease ◽  
Alcohol Withdrawal ◽  
Chronic Liver ◽  
Outpatient Basis ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
The Mean

Background: Alcohol is one of the most common etiology for chronic liver disease. There are several enzymes which remain elevated in both excessive Alcohol consumption and Alcohol induced liver cirrhosis1.  But none is sensitive or specific.  The ratio of Aspartate transaminase (AST) with Alanine transaminase (ALT) is one of the best marker for alcohol liver disease. Current study mainly compares the ratio of AST/ALT with both Alcoholic liver disease and excessive Alcohol consumption patients.Methods: Observational, cross sectional study conducted on 50 patients diagnosed with alcoholic liver disease and 50 patients of alcohol withdrawal syndrome.  Either admitted or seen on outpatient basis at Bangalore medical college and research institute and data was compared among the groups and appropriate statistical methods are applied.Results: The mean ratio of AST/ALT ratio in 50 patients of alcoholic liver disease group was 3.45, whereas the mean ratio in 50 patient of alcohol withdrawal was about 99. When compared statistically this ratio was significant in chronic liver disease group.Conclusions: Most of the patients with heavy alcohol drinking had high AST and alt levels. But ratio of AST/ALT levels was significant high and suggest chronic liver disease secondary to alcohol.

scholarly journals Electrolyzed Hydrogen Water Protects against Ethanol-Induced Cytotoxicity by Regulating Aldehyde Metabolism-Associated Enzymes in the Hepatic Cell Line HepG2

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 801
Author(s):  
Satoshi Yano ◽  
Jinyun Wang ◽  
Shigeru Kabayama ◽  
Taichi Hara
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Molecular Hydrogen ◽  
Toxic Substance ◽  
Excessive Alcohol Consumption ◽  
Hydrogen Water ◽  
Hepatocellular Damage ◽  
Electrolytic Hydrogen ◽  
Excessive Alcohol ◽  
Serious Disease

Excessive alcohol consumption can cause multi-systemic diseases. Among them, alcoholic liver disease is the most frequent and serious disease. Electrolytic hydrogen water (EHW) is produced at the cathode during electrolysis of water and contains a large amount of molecular hydrogen and a low content of platinum nanoparticles with alkaline properties. In this study, we found that EHW inhibits ethanol-induced cytotoxicity by decreasing the intracellular acetaldehyde, a toxic substance produced by ethanol degradation, in hepatocyte cell lines HepG2. Analysis of the mechanism of action revealed that EHW inhibits the metabolism of ethanol to acetaldehyde by suppressing alcohol dehydrogenase. EHW also promotes the metabolism of acetaldehyde to acetic acid by activating aldehyde dehydrogenase, which plays to reduce aldehyde toxicity and intracellular reactive oxygen species in HepG2 cells. These functions were correlated with the concentration of molecular hydrogen in EHW, and were abolished by degassing treatment, suggesting that molecular hydrogen may contribute as a functional factor in the suppression of ethanol-induced hepatocellular damage. Furthermore, hydrogen water with high dissolved hydrogen molecule showed the same hepatocellular protective effect against ethanol as the EHW. These results suggest that EHW may be useful in the prevention of alcoholic 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...

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

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