Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and has been etiologically associated with insulin resistance (IR). The histopathology of NAFLD ranges between simple steatosis and nonalcoholic steatohepatitis (NASH), with or without fibrosis. The aim of the present study was to examine the effect of heparin on steatohepatitis and hepatic-induced nitric oxide synthase (iNOS) expression in mice. Male mice were divided into four groups, which included the normal basal diet (control), high fat (HF) diet, HF diet + heparin (treatment group) and heparin control groups. After eight weeks from the initiation of the experiment, blood was collected and livers were harvested for biochemical analysis and histological studies. Serum levels of aspartate aminotransferase, alanine aminotransferase, hepatic triglyceride (TG) and hydroxyproline, as well as the IR, superoxide anion generation and mRNA expression of the hepatic iNOS enzyme were evaluated. Liver specimens were processed for histopathological and immunohistopathological evaluation. Heparin administration decreased the levels of the liver enzymes, IR, superoxide generation, hepatic TG, hydroxyproline and iNOS expression when compared with the HF diet group. These changes were associated with an improvement in inflammation and fibrosis observed via histopathological examination. Therefore, heparin treatment attenuates hepatic injury in steatohepatitis.
Highlights
Nonalcoholic fatty liver disease (NAFLD) occurs in individuals that have not consumed alcohol in amounts considered harmful to the liver
The current study aimed to examine the effects of heparin, a thrombin inhibitor, on hepatic injury in an experimental model of Nonalcoholic steatohepatitis (NASH) and insulin resistance (IR), via analyzing the effects on hepatic inducible nitric oxide synthase expression and superoxide generation
The increment of these parameters was significantly attenuated in the high fat (HF) + heparin group (P≤0.05; Table I) when compared with the HF diet group
Summary
Nonalcoholic fatty liver disease (NAFLD) occurs in individuals that have not consumed alcohol in amounts considered harmful to the liver. There are two histological patterns of NAFLD: Fatty liver alone and steatohepatitis. Nonalcoholic steatohepatitis (NASH) is defined as lipid accumulation in the liver with evidence of cellular damage, inflammation and varying degrees of scarring or fibrosis [1]. The association between macrovesicular steatosis of the liver and inflammatory changes and fibrosis in obese individuals has been reported for several decades [2]. The spectrum of this condition ranges between silent nonalcoholic fatty liver disease and chronic liver disease with complications. Animal models indicate that the liver may accumulate lipids within a few weeks or even a few days [3]
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