Z-LLY-FMK can attenuate hepatocyte apoptosis after bile duct ligation in rat

Shyr Ming Sheen-Chen, Hsin Tsung Ho, Kuo Sheng Hung, Hock Liew Eng

Research output: Contribution to journalArticle

2 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)2975-2979
Number of pages5
JournalDigestive Diseases and Sciences
Volume53
Issue number11
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Fingerprint

Bile Ducts
Common Bile Duct
Ligation
Hepatocytes
Apoptosis
Calpain
benzyloxycarbonyl-leucyl-glucyl-tyrosine fluoromethyl ketone
Poisons
Cholestasis
Dimethyl Sulfoxide
Bile Acids and Salts
Sprague Dawley Rats
Liver

Keywords

  • Apoptosis
  • Obstructive jaundice
  • Z-LLY-FMK
  • ZFA-FMK

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Z-LLY-FMK can attenuate hepatocyte apoptosis after bile duct ligation in rat. / Sheen-Chen, Shyr Ming; Ho, Hsin Tsung; Hung, Kuo Sheng; Eng, Hock Liew.

In: Digestive Diseases and Sciences, Vol. 53, No. 11, 11.2008, p. 2975-2979.

Research output: Contribution to journalArticle

Sheen-Chen, Shyr Ming ; Ho, Hsin Tsung ; Hung, Kuo Sheng ; Eng, Hock Liew. / Z-LLY-FMK can attenuate hepatocyte apoptosis after bile duct ligation in rat. In: Digestive Diseases and Sciences. 2008 ; Vol. 53, No. 11. pp. 2975-2979.
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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. 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.",
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N2 - 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.

AB - 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.

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