Diminazene aceturate alleviated lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice

Diminazene aceturate (DIZE) has been widely used as an antiprotozoal agent, but recent studies have revealed its anti-inflammatory activities. In the present study, the potential effects of DIZE on lethal inflammatory disorder were investigated in a mouse model with lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis. The results indicated that treatment with DIZE suppressed LPS/D-Gal-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated histopathological damage in liver and improved the survival rate of the experimental animals, these effects were accompanied with inhibited expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Treatment with DIZE also inhibited the activation of caspase-3, -8, -9, reduced the level of cleaved caspase-3, suppressed the phosphorylation of c-jun-N-terminal kinase (JNK) and decreased the count of TUNEL-positive cells. These data suggests that DIZE might have potential value in the prevention of inflammation-based lethal inflammatory liver disorders.