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Effect of ZVAD-fmk on Hepatocyte Apoptosis After Bile Duct Ligation in Rat

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

World J Gastroenterol. 2005 Apr 21;11(15):2330-3.

PMID: 15818747

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4245644	Z-Phe-Ala fluoromethyl ketone			Price

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