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.

CONCLUSION:

These data suggest the inflammatory response from I/R is augmented in livers with NASH histopathology compared with normal liver.

• Authors: Amit D Tevar, Callisia N Clarke, Rebecca Schuster, Jiang Wang, Michael J Edwards, Alex B Lentsch
• Journal: The Journal of surgical research (J Surg Res) Vol. 169 Issue 1 Pg. e7-14 (Jul 2011) ISSN: 1095-8673 [Electronic] United States
• PMID: 21492876 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Methionine
• Peroxidase
• Alanine Transaminase

Topics

• Alanine Transaminase (metabolism)
• Animals
• Diet
• Disease Models, Animal
• Disease Progression
• Fatty Liver (etiology, metabolism, physiopathology)
• Ischemia (metabolism, pathology, physiopathology)
• Liver (blood supply, metabolism, pathology)
• Male
• Methionine (deficiency)
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease
• Peroxidase (metabolism)
• Reperfusion Injury (metabolism, pathology, physiopathology)