Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge

研究成果: 雜誌貢獻文章同行評審

摘要

Background and Aim: Retention and accumulation of toxic hydrophobic bile salts within hepatocytes may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Boc-D-FMK is a cell-permeable irreversible inhibitor of caspase and recent data suggest that it might block the processing of many caspases. The purpose of the present study was to evaluate the possible effect of Boc-D-FMK on hepatocyte apoptosis and on survival rate after bile duct ligation in the rat. Methods: Male Sprague-Dawley rats, weighing 280-300 g were randomized to three groups of eight rats each. Group 1 (OBBOC-D) underwent common bile duct ligation and simultaneous treatment with Boc-D-FMK-fmk (dissolved in dimethylsulfoxide [DMSO]). Group 2 (OBZFA) underwent common bile duct ligation and simultaneous treatment with ZFA-fmk (dissolved in DMSO). Group 3 (SHAM) underwent sham operation and simultaneous treatment with the same amount of dimethylsulfoxide (DMSO, n = 4) or the same amount of normal saline (n = 4). After 3 days, liver tissue was harvested for histopathological analysis and measurements of apoptosis. Survival rates were measured in a separate experiment in which animals underwent the same protocol. The animals received endotoxin (15 mg/kg) in the afternoon of the third postoperative day. Animals were observed for 48 h and the survival rates were recorded. Results: When compared with sham operation, common bile duct ligation with ZFA-fmk (placebo) significantly increased hepatocyte apoptosis (P <0.001). When compared with the OBZFA group, Boc-D-FMK significantly diminished the increased hepatocyte apoptosis in the OBBOC-D group (P <0.001). There is no difference in hepatocyte apoptosis (P = 0.05) between OBBOC-D and SHAM groups. After endotoxin challenge, the 48 h survival rates were 100%, 87.5% and 62.5% for the SHAM, OBBOC-D and OBZFA groups, respectively. Conclusions: Boc-D-FMK-fmk effectively attenuated the hepatocyte apoptosis in bile duct-ligated rats and may improve the survival rates after endotoxin challenge.

原文英語
頁(從 - 到)1276-1279
頁數4
期刊Journal of Gastroenterology and Hepatology (Australia)
23
發行號8 PART1
DOIs
出版狀態已發佈 - 2008
對外發佈Yes

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

指紋 深入研究「Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge」主題。共同形成了獨特的指紋。

引用此