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

Abstract

(2013) Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats, Pharmaceutical Biology, 51:10, 1298-1303, DOI: 10.3109/13880209.2013 Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemiareperfusion-induced injury in rats. Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl 4 in rats. Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl 4 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 AE 18.16 versus 141.2 AE 15.28, p ¼ 0.003), aspartate aminotransferase (AST; 225.10 AE 36.54 versus 170.06 AE 27.14, p ¼ 0.007) and hydroxyproline (Hyp; 1.14 AE 0.27 versus 0.62 AE 0.17, p ¼ 0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15 AE 0.16 versus 0.87 AE 0.15, p ¼ 0.003) and increased the activities of superoxide dismutase (SOD; 6.07 AE 0.95 versus 7.75 AE 1.12, p ¼ 0.007). rBPTI reduced the production of cytokines of IL-1b and TGF-b. 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 CCl 4 , which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.