Effects of free radical scavenger on acute liver injury induced by d‐galactosamine and lipopolysaccharide in rats

Abstract

Acute severe liver injury still has a high mortality rate. Acute liver injury induced by a coadministration of d-galactosamine (GalN) and lipopolysaccharide (LPS) is an experimental model of fulminant hepatitis in rats. Our aim is to investigate the effects of free radical scavenger on the injury induced by GalN/LPS in rats. Free radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) was twice injected into rats 5 min before and 60 min after the GalN/LPS injection. Liver injury was biochemically and histologically assessed. The survival rate was examined 72 h after the intoxication. In the GalN/LPS-treated rats, a marked elevation in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels was observed. On the other hand, edaravone significantly inhibited the elevation in serum AST and ALT levels. The efficacy of edaravone was also confirmedby histological analysis. Edaravone lowered the levels of proinflammatory cytokines TNF-alpha mRNA and interleukin-6 mRNA expression, antioxidative enzyme heme oxygenase-1 protein and myeloperoxidase activity, a marker of neutrophil infiltration, in rat livers. In addition, edaravone reduced the mortality rate in GalN/LPS-treated rats as compared to the rats without edaravone treatment. Free radical scavenger edaravone effectively ameliorated the liver injury induced by the GalN/LPS administration in rats, not only by attenuating oxidative stress, but also by reducing the expression of proinflammatory cytokines.