title: Z-LLY-FMK can attenuate hepatocyte apoptosis after bile duct ligation in rat.
abstract: BACKGROUND
  Cholestasis leading to retention and accumulation of toxic hydrophobic bile salts within hepatocytes may cause hepatocyte toxicity by inducing apoptosis. Calpains have been found to be involved in apoptosis of many cell systems. This study is designed with the aim of evaluating the possible effect of Z-LLY-FMK (a calpain inhibitor) on hepatocyte apoptosis after bile duct ligation in rat.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized to five groups. Group 1 (C) underwent sham operation. Group 2 (CDMSO) underwent Sham operation and simultaneous treatment with dimethylsulfoxide (DMSO). Group 3 (OB) underwent common bile duct ligation. Group 4 (OBZLLY) underwent common bile duct ligation and simultaneous treatment with Z-LLY-FMK. Group 5 (OBZFA) underwent common bile duct ligation and simultaneous treatment with ZFA-FMK. After 3 days, liver tissue was harvested for histopathologic analysis and apoptosis measurements.
  
  
  RESULTS
  When compared with sham operation groups, increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation. Following administration of Z-LLY-FMK, the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation were significantly diminished (P < 0.001 and P < 0.001). Moreover, administration of ZFA failed to show the same phenomenon (P = 0.9 and 0.987).
  
  
  CONCLUSIONS
  Significantly increased hepatocyte apoptosis and ductular proliferation occurred after common bile duct ligation. The administration of Z-LLY-FMK could effectively diminish the hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas the administration of ZFA-FMK failed to show the same effect.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, Taiwan, smsheen@yahoo.com.
authors.forename: Shyr-Ming
authors.initials: SM
authors.lastname: Sheen-Chen
authors.forename: Hsin-Tsung
authors.initials: HT
authors.lastname: Ho
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Hung
authors.forename: Hock-Liew
authors.initials: HL
authors.lastname: Eng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001652:Bile Ducts / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002154:Calpain / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D041781:Jaundice, Obstructive / Q000188:drug therapy / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002154:Calpain