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

@article{Thurman1998TheRO,
  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},
  year={1998},
  volume={13}
}
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)‐α antibody markedly decreased EtOH‐induced liver injury and increased TNF‐mRNA. These findings led to… 
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It is demonstrated that GdCl3 prevents alcohol‐induced liver injury and suggest strongly that Kupffer cells participate in the early phases of the disease process and might represent a new approach to clinical management of alcohol‐ induced liver injury.
Antibiotics prevent liver injury in rats following long-term exposure to ethanol.
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Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.
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The results indicate that chronic ethanol causes hypoxia at the cellular level in rat liver in vivo and lend support to the hypothesis that Hypoxia is involved in mechanisms of early alcoholic liver injury.
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TLDR
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TLDR
In cultured Kupffer cells, nimodipine largely prevented the elevation in [Ca2+]i caused by lipopolysaccharide (LPS), and this results indicate that nimmodipine prevents alcoholic hepatitis, possibly by inhibition of endotoxin‐mediated Kupfer cell activation.
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TLDR
The results suggest that early in chronic alcohol consumption, the immune system may be stimulated by ethanol, and that during studies of ethanol-induced changes in immune system function, close attention must be given to potentially confounding effects of the diet.
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