Literature DB >> 16706830

Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency.

Richard Kirsch1, Vivian Clarkson, Robert C Verdonk, Adrian D Marais, Enid G Shephard, Bernard Ryffel, Pauline de la M Hall.   

Abstract

BACKGROUND AND AIMS: Intestinal endotoxin (lipopolysaccharide) is thought to contribute to liver injury in both alcoholic and nonalcoholic steatohepatitis (NASH). Tumor necrosis factor alpha (TNFalpha) is an important mediator of this process and is considered central to the inflammatory response in NASH. This study aimed to investigate the effects of lipopolysaccharide on liver injury in the methionine choline deficient (MCD) nutritional model of NASH, and to determine if TNFalpha is required for the development of steatohepatitis in this model.
METHOD: Male C57/BL6 mice received a MCD diet for 4 weeks, whilst a control group received an identical diet supplemented with 0.2% choline bitartrate and 0.3% methionine. At 4 weeks, mice received either an intraperitoneal injection of lipopolysaccharide (0.5 microg/g body mass) or sterile saline, and were killed 24 h thereafter. In a separate study, TNFalpha knockout and wild type C57BL/6 mice received either MCD or control diets for 4 weeks. Serum transaminase levels, liver histology (steatosis, inflammation and apoptosis), hepatic triglyceride concentration and hepatic lipid peroxidation products (conjugated dienes, lipid hydroperoxides and thiobarbituric reactive substances, free and total) were evaluated.
RESULTS: Intraperitoneal administration of lipopolysaccharide augmented serum alanine aminotransferase (ALT) levels (P<0.02), hepatic inflammation (P<0.025), apoptosis (P<0.01) and free thiobarbituric acid reactive substances (P<0.025) in MCD mice. TNFalpha knockout mice fed the MCD diet developed steatohepatitis with histological and biochemical changes similar to those seen in wild type counterparts.
CONCLUSIONS: Lipopolysaccharide augments liver injury in MCD mice, and TNFalpha is not required for the development of steatohepatitis in MCD mice.

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Year:  2006        PMID: 16706830     DOI: 10.1111/j.1440-1746.2005.04220.x

Source DB:  PubMed          Journal:  J Gastroenterol Hepatol        ISSN: 0815-9319            Impact factor:   4.029


  18 in total

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Review 7.  Intestinal Barrier and Permeability in Health, Obesity and NAFLD.

Authors:  Piero Portincasa; Leonilde Bonfrate; Mohamad Khalil; Maria De Angelis; Francesco Maria Calabrese; Mauro D'Amato; David Q-H Wang; Agostino Di Ciaula
Journal:  Biomedicines       Date:  2021-12-31

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9.  IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.

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10.  Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment.

Authors:  Suzanne M de la Monte; Ming Tong; Margot Lawton; Lisa Longato
Journal:  Mol Neurodegener       Date:  2009-12-24       Impact factor: 14.195

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