Brief Reports
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2005; 11(15): 2330-2333
Published online Apr 21, 2005. doi: 10.3748/wjg.v11.i15.2330
Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat
Shyr-Ming Sheen-Chen, Hsin-Tsung Ho, Wei-Jen Chen, Hock-Liew Eng
Shyr-Ming Sheen-Chen, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, College of Medicine, Chang Gung University, Taiwan China
Hsin-Tsung Ho, Department of Laboratory Medicine, Mackay Memorial Hospital, Taiwan China
Wei-Jen Chen, Hock-Liew Eng, Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung, College of Medicine, Chang Gung University, Taiwan China
Author contributions: All authors contributed equally to the work.
Supported by the grant NSC 89-2314-B-182A-165 from the National Science Council of Taiwan China
Correspondence to: Dr. Shyr-Ming Sheen-Chen, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan China. smsheen@yahoo.com
Telephone: +886-7-7317123
Received: August 14, 2004
Revised: August 15, 2004
Accepted: September 30, 2004
Published online: April 21, 2005
Abstract

AIM: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Z-Val-Ala-Asp (OMe)-fluoromethyl ketone (ZVAD-fmk) is a cell-permeable irreversible inhibitor of caspase. The purpose of this study was to evaluate the possible effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in the rat.

METHODS: Male Sprague-Dawley rats, weighing 250-300 g, were randomized to five groups of five rats each. Group 1 underwent common bile duct ligation and simultaneous treatment with ZVAD-fmk (dissolved in dimethylsulfoxide (DMSO)). Group 2 underwent common bile duct ligation and simultaneous treatment with Z-Phe-Ala-fluoromethyl ketone ( ZFA-fmk, dissolved in DMSO). Group 3 underwent sham operation and simultaneous treatment with the same amount of DMSO. Group 4 underwent sham operation and simultaneous treatment with the same amount of normal saline. Group 5 underwent common bile duct ligation without other manipulation. After three days, liver tissue was harv-ested for histopathologic analysis and measurements of apoptosis.

RESULTS: When compared with sham operation, common bile duct ligation significantly increased hepatocyte apoptosis (P = 0.008) and ductular proliferation (P = 0.007). ZVAD-fmk significantly diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (P = 0.008 and P = 0.007, respectively). ZFA did not show the same effects.

CONCLUSION: Hepatocyte apoptosis and ductular proliferation significantly increased after common bile duct ligation. ZVAD-fmk effectively diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas ZFA-fmk did not.

Keywords: Apoptosis; Obstructive jaundice; ZVAD-fmk; ZFA