Intraperitoneal Administration of Fetuin-A Attenuates d-Galactosamine/Lipopolysaccharide-Induced Liver Failure in Mouse

BACKGROUND: Fulminant hepatic failure (FHF) is a devastating syndrome, which sometimes results in death or liver transplantation, in which inflammation would aggravate the development of fetuin-A which would act as an anti-inflammatory factor and may be an available approach to attenuate FHF. AIMS: The purpose of this study was to investigate the effects of fetuin-A on d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced liver failure in mice. METHODS: A mouse model of FHF induced by d-GalN/LPS was established and fetuin-A was injected intraperitoneally prior to d-GalN/LPS treatment. At different time points after d-GalN/LPS intervention, serum TNF-α and IL-6 levels were measured by ELISA. Fetuin-A mRNA and protein expression in liver tissues was assessed by RT-PCR, Western blotting and immunohistochemical staining. Besides, an observation of liver tissue injury, the apoptosis of hepatocytes, was analyzed by TUNEL assay. RESULTS: Expression of fetuin-A mRNA and protein in liver tissue were significantly and gradually decreased after d-GalN/LPS administration. A pre-intervention of exogenous fetuin-A significantly improved the liver function, decreased TNF-α and IL-6 expression in peripheral blood, and liver tissue inhibited hepatocyte apoptosis responded to d-GalN/LPS induction so as to decrease the mortality rates of FHF mouse. Meanwhile, fetuin-A was negatively correlated with the hepatic pathological score and TNF-α protein staining in FHF mouse. CONCLUSIONS: An intraperitoneal injection of fetuin-A attenuates d-GalN/LPS-induced FHF in mice. Fetuin-A might be a protective agent of liver damage partly through inhibiting liver inflammatory response and hepatocyte apoptosis.