• Corpus ID: 39083280

The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury.

  title={The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury.},
  author={Ronald G. Thurman and Blair U. Bradford and Yuji Iimuro and Kathryn T. Knecht and Gavin E. Arteel and Ming Yin and Henry D. Connor and Chantal Wall and James A. Raleigh and Moritz von Frankenberg and Y Adachi and Donald T. Forman and David A. Brenner and Maria B. Kadiiska and Ronald P. Mason},
  journal={Journal of gastroenterology and hepatology},
  volume={13 Suppl},
Previous research from this laboratory using a continuous enteral ethanol (EtOH) administration model demonstrated that Kupffer cells are pivotal in the development of EtOH-induced liver injury. When Kupffer cells were destroyed using gadolinium chloride (GdCl3) or the gut was sterilized with polymyxin B and neomycin, early inflammation due to EtOH was blocked. Anti-tumour necrosis factor (TNF)-alpha antibody markedly decreased EtOH-induced liver injury and increased TNF-mRNA. These findings… 
Cinnamon extract protects against acute alcohol-induced liver steatosis in mice.
Data show that an alcohol extract of cinnamon bark may protect the liver from acute alcohol-induced steatosis through mechanisms involving the inhibition of MyD88 expression.
Role of ICAM-1 in chronic ethanol consumption-enhanced liver injury after gut ischemia-reperfusion in rats.
It is suggested that chronic EtOH consumption enhances gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury in the pericentral region and terminal hepatic venules via an enhanced hepatic expression of ICAM-1.
Metformin prevents alcohol-induced liver injury in the mouse: Critical role of plasminogen activator inhibitor-1.
Findings suggest a novel mechanism of action for metformin and identify a new role of PAI-1 in hepatic injury caused by ethanol.
Inhibition of the mitochondrial permeability transition by cyclosporin A prevents pyrazole plus lipopolysaccharide-induced liver injury in mice.
It is shown that cyclosporin A does protect mice from the pyrazole plus LPS-induced liver toxicity by preventing the MPT and release of cytochrome c and decreasing mitochondrial oxidative stress, and indicates that mitochondria are the critical targets of pyrazolesplus LPS in mediating liver injury.
Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide‐induced liver injury caused by ethanol in mice
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PKCε contributes to chronic ethanol-induced steatosis in mice but not inflammation and necrosis.
This study identifies a novel potential mechanism where EtOH, independent of steatosis, can contribute to liver damage and suggests that PAI-1 and fibrin accumulation may be at the center of this PKCε-independent pathway.
Intestinal endotoxemia as a pathogenetic mechanism in liver failure.
  • Dewu Han
  • Medicine
    World journal of gastroenterology
  • 2002
The viewpoint of SLI induced by the second hit on liver inflicted by IETM suggests that medical professionals should attach great importance to both PLI and SLI caused by IETS, to adjust the function of KS(s) and eliminate endotoxemia of the patient.
Ethanol and arachidonic acid synergize to activate Kupffer cells and modulate the fibrogenic response via tumor necrosis factor α, reduced glutathione, and transforming growth factor β–dependent mechanisms
These results unveil synergism between ethanol and AA to the mechanism whereby KC mediate ECM remodeling and suggest that even if chronic ethanol consumption sensitizes HSC to up‐regulate anti‐fibrogenic signals, their effects are blunted by a second “hit” such as AA.
The presence of p47phox in liver parenchymal cells is a key mediator in the pathogenesis of alcoholic liver steatosis.
It is suggested that p47phox in parenchymal cells plays a critical role in the pathogenesis of ALD through mechanisms involving ADRP, FASN, and ACACA as well as from alcohol-induced NF-κB activation.
Arachidonic acid stimulates TNFα production in Kupffer cells via a reactive oxygen species-pERK1/2-Egr1-dependent mechanism.
  • F. J. Cubero, N. Nieto
  • Biology, Medicine
    American journal of physiology. Gastrointestinal and liver physiology
  • 2012
This study unveils the mechanism whereby arachidonic acid and ethanol increase TNFα production in Kupffer cells, thus contributing to alcoholic liver disease.