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. MATERIALS AND 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). CONCLUSION: 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.
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. MATERIALS AND 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). CONCLUSION: 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: C Benz; S Angermüller; U Töx; P Klöters-Plachky; H D Riedel; P Sauer; W Stremmel; A Stiehl Journal: J Hepatol Date: 1998-01 Impact factor: 25.083