Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl4 in rats.Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl4 at a dose of 2 ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100 mg/kg) daily for the next 4 weeks.Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7 ± 18.16 versus 141.2 ± 15.28, p = 0.003), aspartate aminotransferase (AST; 225.10 ± 36.54 versus 170.06 ± 27.14, p = 0.007) and hydroxyproline (Hyp; 1.14 ± 0.27 versus 0.62 ± 0.17, p = 0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15 ± 0.16 versus 0.87 ± 0.15, p = 0.003) and increased the activities of superoxide dismutase (SOD; 6.07 ± 0.95 versus 7.75 ± 1.12, p = 0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl4, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.