Apoptosis

, Volume 18, Issue 5, pp 547–555

Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury

Authors

    • Liver Disease Center, Sheba Medical Center
    • Liver Research Laboratory
    • Sackler School of Medicine, Tel Aviv University
  • Y. Issan
    • Research Laboratory, Felsenstein Medical Research Center
  • Y. Katz
    • Department of Surgery ARabin Medical Center, Beilinson Hospital
  • M. Sultan
    • Liver Research Laboratory
  • M. Safran
    • Liver Research Laboratory
  • Laniado-Schwartzman Michal
    • Departments of PharmacologyNew York Medical College
  • G. Abraham Nader
    • Departments of PharmacologyJoan C. Edwards School of Medicine, Marshall University
  • R. Kornowski
    • Research Laboratory, Felsenstein Medical Research Center
  • F. Grief
    • Department of Surgery ARabin Medical Center, Beilinson Hospital
  • O. Pappo
    • Department of HistopathologySheba Medical Center
  • E. Hochhauser
    • Sackler School of Medicine, Tel Aviv University
Original Paper

DOI: 10.1007/s10495-013-0814-x

Cite this article as:
Ben-Ari, Z., Issan, Y., Katz, Y. et al. Apoptosis (2013) 18: 547. doi:10.1007/s10495-013-0814-x

Abstract

Ischemia/reperfusion (I/R) injury is the main cause of primary graft dysfunction of liver allografts. Cobalt-protoporphyrin (CoPP)–dependent induction of heme oxygenase (HO)-1 has been shown to protect the liver from I/R injury. This study analyzes the apoptotic mechanisms of HO-1-mediated cytoprotection in mouse liver exposed to I/R injury. HO-1 induction was achieved by the administration of CoPP (1.5 mg/kg body weight i.p.). Mice were studied in in vivo model of hepatic segmental (70 %) ischemia for 60 min and reperfusion injury. Mice were randomly allocated to four main experimental groups (n = 10 each): (1) A control group undergoing sham operation. (2) Similar to group 1 but with the administration of CoPP 72 h before the operation. (3) Mice undergoing in vivo hepatic I/R. (4) Similar to group 3 but with the administration of CoPP 72 h before ischemia induction. When compared with the I/R mice group, in the I/R+CoPP mice group, the increased hepatic expression of HO-1 was associated with a significant reduction in liver enzyme levels, fewer apoptotic hepatocytes cells were identified by morphological criteria and by immunohistochemistry for caspase-3, there was a decreased mean number of proliferating cells (positively stained for Ki67), and a reduced hepatic expression of: C/EBP homologous protein (an index of endoplasmic reticulum stress), the NF-κB’s regulated genes (CIAP2, MCP-1 and IL-6), and increased hepatic expression of IκBa (the inhibitory protein of NF-κB). HO-1 over-expression plays a pivotal role in reducing the hepatic apoptotic IR injury. HO-1 may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation.

Keywords

Heme oxygenase-1Cobalt-protoporphyrinNuclear factor-kappaB (NF-κB)Ischemia reperfusion injuryLiver

Copyright information

© Springer Science+Business Media New York 2013