Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced acute injury in mice

Abstract

OBJECTIVES: Toxicity caused by pharmacological and chemical substances, including carbon tetrachloride (CCl(4)), is a major pathological factor for liver injury. Therefore, strategies to prevent toxicity are needed for maintaining a healthy liver. This study was designed to determine whether recombinant bovine pancreatic trypsin inhibitor (rBPTI), a non-specific serine protease inhibitor, prevents CCl(4)-induced liver injury in mice. METHODS: Mice were treated with CCl(4) in the presence or absence of co-treatment with rBPTI. Liver sections were prepared for histopathological assessment. Liver function was evaluated by detecting serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver index. Liver oxidative stress and inflammation were examined by detecting the liver malondialdehyde level and glutathione and superoxide dismutase activity, and serum tumour necrosis factor-alpha level, respectively. KEY FINDINGS: CCl(4) induced hepatocyte necrosis, inflammatory cell infiltration and fatty degeneration, which were ameliorated by co-treatment with rBPTI in a concentration-dependent manner. Furthermore, rBPTI prevented CCl(4)-induced disruption of liver function. Importantly, rBPTI reduced CCl(4)-induced liver oxidative stress response and pro-inflammatory cytokine production. CONCLUSIONS: These results indicated that rBPTI exerted a protective effect on CCl(4)-induced liver injury in mice. Thus, rBPTI may have potential application for prevention of liver injury induced by metabolism of drugs and toxic substances.