Protective effects of ulinastatin on acute liver failure induced by lipopolysaccharide/D-galactosamine.

ABSTRACT

BACKGROUND: Although treatment of acute liver failure has been improved significantly recently, the survival rate of acute liver failure is only 5-20%. Therefore, prevention and treatment of acute liver failure are still urgent issues in the field of liver disease. AIMS: It has been demonstrated that ulinastatin could attenuate acute injury of internal organs from endotoxin. This study evaluates whether ulinastatin can prevent and/or attenuate acute liver failure induced by the combination of lipopolysaccharide and D-galactosamine (LPS/D-gal). METHODS: Sprague-Dawley rats were employed to induce acute liver failure by injection of LPS/D-gal. The liver function, inflammatory factors, oxidative stress index, and hepatic histopathological alteration were examined in the rats with and without ulinastatin treatment. RESULTS: In rats treated with LPS/D-gal, there were increases in the levels of ALT and AST in the serum and levels of malondialdehyde and inducible nitric oxide synthase in liver tissues. Moreover, the levels of antioxidants such as superoxide dismutase and glutathione peroxidase were reduced in the liver. Furthermore, inflammatory factors (TNF-alpha and IL-6) and apoptotic enzyme (caspase-3) were increased in the respective serum and liver of rats treated with LPS/D-gal. However, pre-treatment of ulinastatin significantly reversed all of these parameters in the rats that received LPS/D -gal alone. CONCLUSIONS: The finding in this study suggests that ulinastatin could be a potential agent for prevention and treatment of acute liver injury induced by LPS/D-gal.