Role of oxidative stress and Kupffer cells in hepatic fibrosis.

Although non-alcoholic steatohepatitis (NASH) has become a common disease worldwide, its pathogenesis remains unclear. Establishment of a proper animal model is a prerequisite for analyzing the molecular mechanism of this disease. A NASH model has been developed using rabbits fed a high-fat diet. These rabbits developed prominent fatty changes in hepatocytes. Hepatic fibrosis was seen around hepatocytes and the portal vein area. Apoptotic hepatocytes, which were rare in the intact liver, appeared in the liver of high-fat diet-fed rabbits. It is speculated that Kupffer cells/macrophages may play an important role in triggering the generation of oxidative stress in this model. Thus, this rabbit model is proposed for use in the molecular analysis of human NASH.