title: Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Tianjin Hongqiao Hospital, Tianjin, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.forename: Bo
authors.initials: B
authors.lastname: Lv
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000517:prevention & control; D006909:Hydroxyproline / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009336:Necrosis; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D020011:Protective Agents; D011994:Recombinant Proteins; D017392:Thiobarbituric Acid Reactive Substances; D016212:Transforming Growth Factor beta; D007611:Aprotinin; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline