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Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency.
J Gastroenterol Hepatol. 2006 Jan; 21(1 Pt 1):174-82.JG

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.

Authors+Show Affiliations

Department of Anatomical Pathology, Cape Heart Center and Medical Research Council, Cape Town, South Africa. rich@chempath.uct.ac.zaNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16706830

Citation

Kirsch, Richard, et al. "Rodent Nutritional Model of Steatohepatitis: Effects of Endotoxin (lipopolysaccharide) and Tumor Necrosis Factor Alpha Deficiency." Journal of Gastroenterology and Hepatology, vol. 21, no. 1 Pt 1, 2006, pp. 174-82.
Kirsch R, Clarkson V, Verdonk RC, et al. Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency. J Gastroenterol Hepatol. 2006;21(1 Pt 1):174-82.
Kirsch, R., Clarkson, V., Verdonk, R. C., Marais, A. D., Shephard, E. G., Ryffel, B., & de la M Hall, P. (2006). Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency. Journal of Gastroenterology and Hepatology, 21(1 Pt 1), 174-82.
Kirsch R, et al. Rodent Nutritional Model of Steatohepatitis: Effects of Endotoxin (lipopolysaccharide) and Tumor Necrosis Factor Alpha Deficiency. J Gastroenterol Hepatol. 2006;21(1 Pt 1):174-82. PubMed PMID: 16706830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency. AU - Kirsch,Richard, AU - Clarkson,Vivian, AU - Verdonk,Robert C, AU - Marais,Adrian D, AU - Shephard,Enid G, AU - Ryffel,Bernard, AU - de la M Hall,Pauline, PY - 2006/5/19/pubmed PY - 2007/8/7/medline PY - 2006/5/19/entrez SP - 174 EP - 82 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 21 IS - 1 Pt 1 N2 - 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. SN - 0815-9319 UR - https://www.unboundmedicine.com/medline/citation/16706830/Rodent_nutritional_model_of_steatohepatitis:_effects_of_endotoxin__lipopolysaccharide__and_tumor_necrosis_factor_alpha_deficiency_ L2 - https://doi.org/10.1111/j.1440-1746.2005.04220.x DB - PRIME DP - Unbound Medicine ER -