title: The effect of hepatic ischemia reperfusion injury in a murine model of nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) refers to an increasingly diagnosed condition involving triglyceride accumulation into hepatocytes resulting in a broad spectrum of liver injury. The progression of NAFLD, a relatively benign condition, to nonalcoholic steatohepatitis (NASH) involves the hepatic infiltration of inflammatory cells and subsequent hepatocellular injury. Ischemia/reperfusion (I/R) injury of the liver is a major complication of liver resection, hepatic trauma, and liver transplantation. To date, there have been no studies that have evaluated the effects of hepatic I/R on models of NASH.
  
  
  OBJECTIVE
  Evaluate the effects of hepatic I/R on a mouse model of NASH.
  
  
  METHODS
  A mouse model of progressive NASH was developed and evaluated using C57BL/6 mice fed a methionine choline deficient diet for 3, 6, 9, and 12 wk. Mice subsequently underwent 90 min of partial hepatic ischemia with reperfusion of 1, 4, and 8 h. Mice were sacrificed after the indicated periods, and blood and liver samples were taken for analysis.
  
  
  RESULTS
  Mice fed the MCD diet showed a rapid induction of hepatic steatosis, inflammation, and fibrosis by 3 wk that persisted over the 12-wk period of diet, as demonstrated by histologic examination, alanine aminotransferase (ALT), and liver content of myeloperoxidase (MPO). The response to I/R in livers with progressive NASH fed MCD diet for 3, 6, 9, and 12 wk showed marked neutrophil recruitment and hepatocyte necrosis.
  
  
  CONCLUSIONS
  These data suggest the inflammatory response from I/R is augmented in livers with NASH histopathology compared with normal liver.
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA. amit.tevar@uc.edu
authors.forename: Amit D
authors.initials: AD
authors.lastname: Tevar
authors.forename: Callisia N
authors.initials: CN
authors.lastname: Clarke
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schuster
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D008715:Methionine; D009195:Peroxidase; D000410:Alanine Transaminase