scholarly journals Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: A critical role for E-selectin

Hepatology ◽  
2013 ◽  
Vol 58 (5) ◽  
pp. 1814-1823 ◽  
Author(s):  
Adeline Bertola ◽  
Ogyi Park ◽  
Bin Gao
Keyword(s):  
Liver Injury ◽  
Critical Role ◽  
Neutrophil Infiltration ◽  
Ethanol Feeding ◽  
Binge Ethanol

scholarly journals Amelioration of Ethanol-Induced Hepatitis by Magnesium Isoglycyrrhizinate through Inhibition of Neutrophil Cell Infiltration and Oxidative Damage

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Wang ◽  
Zhenzhen Zhang ◽  
Xia Wang ◽  
Dan Qi ◽  
Aijuan Qu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Neutrophil Infiltration ◽  
Cytokines And Chemokines ◽  
Flow Cytometric ◽  
Ethanol Feeding ◽  
Binge Ethanol ◽  
Magnesium Isoglycyrrhizinate

Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. There is no effective treatment to prevent the disease progression. Magnesium isoglycyrrhizinate (MgIG) showed potent anti-inflammatory, antioxidant, and hepatoprotective activities and was used for treating liver diseases in Asia. In this study, we examined whether MgIG could protect mice against alcohol-induced liver injury. The newly developed chronic plus binge ethanol feeding model was used to study the role of MgIG in ALD. Serum liver enzyme levels, H&E staining, immunohistochemical staining, flow cytometric analysis, and real-time PCR were used to evaluate the liver injury and inflammation. We showed that MgIG markedly ameliorated chronic plus binge ethanol feeding liver injury, as shown by decreased serum alanine transaminase and aspartate aminotransferase levels and reduced neutrophil infiltration. The reason may be attributed to the reduced expression of proinflammatory cytokines and chemokines with the treatment of MgIG. The hepatoprotective effect of MgIG was associated with suppression of neutrophil ROS production as well as hepatocellular oxidative stress. MgIG may play a critical role in protecting against chronic plus binge ethanol feeding-induced liver injury by regulating neutrophil activity and hepatic oxidative stress.

scholarly journals TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration

2015 ◽  
Vol 309 (1) ◽  
pp. G30-G41 ◽  
Author(s):  
Yoon Seok Roh ◽  
Bi Zhang ◽  
Rohit Loomba ◽  
Ekihiro Seki
Keyword(s):  
Liver Injury ◽  
Alcoholic Hepatitis ◽  
Early Stage ◽  
Neutrophil Infiltration ◽  
Wild Type ◽  
Ethanol Feeding ◽  
Binge Ethanol ◽  
Deficient Mice ◽  
Cxcl1 Expression

Although previous studies reported the involvement of the TLR4-TRIF pathway in alcohol-induced liver injury, the role of TLR2 and TLR9 signaling in alcohol-mediated neutrophil infiltration and liver injury has not been elucidated. Since alcohol binge drinking is recognized to induce more severe form of alcohol liver disease, we used a chronic-binge ethanol-feeding model as a mouse model for early stage of alcoholic hepatitis. Whereas a chronic-binge ethanol feeding induced alcohol-mediated liver injury in wild-type mice, TLR2- and TLR9-deficient mice showed reduced liver injury. Induction of neutrophil-recruiting chemokines, including Cxcl1, Cxcl2, and Cxcl5, and hepatic neutrophil infiltration were increased in wild-type mice, but not in TLR2- and TLR9-deficient mice. In vivo depletion of Kupffer cells (KCs) by liposomal clodronate reduced liver injury and the expression of Il1b, but not Cxcl1, Cxcl2, and Cxcl5, suggesting that KCs are partly associated with liver injury, but not neutrophil recruitment, in a chronic-binge ethanol-feeding model. Notably, hepatocytes and hepatic stellate cells (HSCs) produce high amounts of CXCL1 in ethanol-treated mice. The treatment with TLR2 and TLR9 ligands synergistically upregulated CXCL1 expression in hepatocytes. Moreover, the inhibitors for CXCR2, a receptor for CXCL1, and MyD88 suppressed neutrophil infiltration and liver injury induced by chronic-binge ethanol treatment. Consistent with the above findings, hepatic CXCL1 expression was highly upregulated in patients with alcoholic hepatitis. In a chronic-binge ethanol-feeding model, the TLR2 and TLR9-dependent MyD88-dependent pathway mediates CXCL1 production in hepatocytes and HSCs; the CXCL1 then promotes neutrophil infiltration into the liver via CXCR2, resulting in the development of alcohol-mediated liver injury.

scholarly journals Animals Models of Gastrointestinal and Liver Diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges

2014 ◽  
Vol 306 (10) ◽  
pp. G819-G823 ◽  
Author(s):  
Stephanie Mathews ◽  
Mingjiang Xu ◽  
Hua Wang ◽  
Adeline Bertola ◽  
Bin Gao
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Neutrophil Infiltration ◽  
Alcoholic Liver Injury ◽  
Drinking Patterns ◽  
Excessive Alcohol Consumption ◽  
Ethanol Feeding ◽  
History Of ◽  
Excessive Alcohol ◽  
Binge Ethanol

Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

scholarly journals Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3

Hepatology ◽  
2010 ◽  
Vol 52 (4) ◽  
pp. 1291-1300 ◽  
Author(s):  
Sung Hwan Ki ◽  
Oygi Park ◽  
Mingquan Zheng ◽  
Oriol Morales-Ibanez ◽  
Jay K. Kolls ◽  
...  
Keyword(s):  
Liver Injury ◽  
Murine Model ◽  
Alcoholic Liver Injury ◽  
Signal Transducer ◽  
Interleukin 22 ◽  
Ethanol Feeding ◽  
Transcription 3 ◽  
Binge Ethanol

scholarly journals Obesity and binge alcohol intake are deadly combination to induce steatohepatitis: A model of high-fat diet and binge ethanol intake

2020 ◽  
Vol 26 (4) ◽  
pp. 586-594 ◽  
Author(s):  
Seonghwan Hwang ◽  
Tianyi Ren ◽  
Bin Gao
Keyword(s):  
Liver Injury ◽  
Binge Drinking ◽  
Mouse Models ◽  
High Fat Diet ◽  
Neutrophil Infiltration ◽  
Mitogen Activated Protein Kinase ◽  
High Fat ◽  
Hepatic Expression ◽  
Underlying Mechanisms ◽  
Binge Ethanol

Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (<i>Cxcl1</i>), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of <i>Cxcl1</i> and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.

scholarly journals Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2509 ◽  
Author(s):  
Jing Zhang ◽  
Xin Guo ◽  
Taiji Hamada ◽  
Seiya Yokoyama ◽  
Yuka Nakamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Critical Role ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Fibrotic Liver ◽  
Intrahepatic Bile Ducts ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

scholarly journals Hepatoprotective Effects of Heracleum candicans Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110295
Author(s):  
Jie Li ◽  
Dan Song ◽  
Bintao Zhang ◽  
Jinwei Guo ◽  
Wenping Li ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Neutrophil Infiltration ◽  
Antioxidant Enzyme Activity ◽  
Necrosis Factor Alpha ◽  
Heracleum Candicans ◽  
The Face ◽  
Factor Alpha ◽  
Necrosis Factor

Purpose: To determine the hepatoprotective mechanisms of Heracleum candicans in rats with acute liver injury induced by carbon tetrachloride (CCl4). Methods: Rats were intragastrically administered H candicans twice a day for 14 consecutive days and were intraperitoneally challenged with CCl4. Alanine aminotransferase and aspartate aminotransferase were measured to indicate liver injury. Malondialdehyde antioxidant enzyme activity and tumor necrosis factor-alpha and interleukin 6 secretion were measured as liver injury indicators. Histopathological tests were conducted to determine whether H candicans ameliorated liver injury. Results: CCl4-induced liver injury led to significant increases in liver injury biochemical indicators transaminase and malondialdehyde activities. H candicans pretreatments inhibited these increases. Pathological sections in pretreated samples exhibited reduced vacuole formation, neutrophil infiltration, and necrosis. Conclusion: H candicans increases the antioxidant capacity of the liver and maintains hepatocyte function in the face of CCl4-induced injury.

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