FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers

Kwan Man, Kevin T. Ng, Kin Wah Lee, Chung Mau Lo, Chris K. Sun, Xian Liang Li, Yi Zhao, Joanna W. Ho, Sheung Tat Fan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Hepatic ischemia-reperfusion injury is an inevitable consequence during liver surgery. The outcome is particularly poor in cirrhotic livers, which are more prone to hepatic ischemia-reperfusion injury. We aim to study whether FTY720 could attenuate hepatic ischemia-reperfusion injury both in normal and in cirrhotic livers. We applied a 70% liver-ischemia (60 min) model in rats with normal or cirrhotic livers. FTY720 was given 20 min before ischemia and 10 min before reperfusion (1 mg/kg, i.v.). Liver tissues and blood were sampled at 20 min, 60 min, 90 min, 6 h and 24 h after reperfusion for detection of MAPK-Egr-1, Akt pathways and caspase cascade. Hepatic ultrastructure and apoptosis were also compared. FTY720 significantly improved liver function in the rats with normal and cirrhotic livers. Akt pathway was activated at 6 and 24 h after reperfusion. FTY720 significantly down-regulated Egr-1, ET-1, iNOS and MIP-2 accompanied with up-regulation of A20, IL-10, HO-1 and Hsp70. MAPK (Raf-MEK-Erk) pathway was down-regulated. Hepatic ultrastructure was well maintained and fewer apoptotic liver cells were found in the FTY720 groups. In conclusion, FTY720 attenuates ischemia-reperfusion injury in both normal and cirrhotic livers by activation of cell survival Akt signaling and down-regulation of Egr-1 via Raf-MEK-Erk pathway.
Original languageEnglish
Pages (from-to)40-49
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Jan 2005
Externally publishedYes

Keywords

  • Akt
  • FTY720
  • Ischemia-reperfusion injury
  • Liver cirrhosis
  • MAPK

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this