Potential role of catalase in mice with lipopolysaccharide/D‐galactosamine‐induced fulminant liver injury

Abstract

Lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-Gal)-sensitized mice is a well-established animal model widely used in exploring the pathogenesis of fulminant hepatitis. Increasing evidence has indicated that reactive oxygen species (ROS)-induced oxidative injury may be involved in LPS/D-Gal-induced hepatitis. Catalase (CAT) is a major antioxidant enzyme while aminotriazole (ATZ) is commonly used as a CAT inhibitor. In the present study, the effects of ATZ on LPS/D-Gal-induced liver injury were investigated. Fuliminant liver injury was induced by intraperitoneal injection of LPS combined with D-Gal, ATZ was administrated 0.5 h prior to LPS/D-Gal challenge. The degree of liver injury, the level of hepatic oxidative stress, the grade of hepatic apoptosis and the survival of experimental animals were determined. Our experimental data showed that treatment with ATZ significantly enhanced LPS/D-Gal-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT), exacerbated the hepatic histopathological abnormality and decreased the survival rate of experimental animals. ATZ inhibited the activity of CAT, increased the content of H2 O2 and the levels of malondialdehyde (MDA) in liver tissues. In addition, treatment with ATZ also enhanced LPS/D-Gal-induced hepatic apoptosis as evidenced by increased caspases activities in liver tissues and increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in liver sections. These findings suggested that CAT might be involved in the progression of LPS/D-Gal-induced fulminant liver injury.