Journal of Molecular Medicine

, Volume 77, Issue 8, pp 577–592

Therapeutic approaches for ischemia/reperfusion injury in the liver

  • Chenguang Fan
  • Ralf M. Zwacka
  • John F. Engelhardt
Original Article

DOI: 10.1007/s001099900029

Cite this article as:
Fan, C., Zwacka, R. & Engelhardt, J. J Mol Med (1999) 77: 577. doi:10.1007/s001099900029


Organ injury caused by transient ischemia followed by reperfusion is associated with a number of clinically and environmentally induced conditions. Ischemia/reperfusion (I/R) conditions arise during surgical interventions such as organ transplantation and coronary bypass surgery, and in diseases such as stroke and cardiac infarct. The destructive effects of I/R arise from the acute generation of reactive oxygen species subsequent to reoxygenation, which inflict direct tissue damage and initiate a cascade of deleterious cellular responses leading to inflammation, cell death, and organ failure. This review summarizes existing and potential approaches for treatment that have been developed from research using model systems of I/R injury. Although I/R injury in the liver is emphasized, other organ systems share similar pathophysiological mechanisms and therapeutic approaches. We also review current knowledge of the molecular events controlling cellular responses to I/R injury, such as activation of AP-1 and NF-κB pathways. Therapeutic strategies aimed at ameliorating I/R damage are focused both on controlling ROS generated at the time of oxygen reperfusion and on intervening in the activated signal transduction cascades. Potential therapies include pharmacological treatment with small molecules, antibodies to cytokines, or free-radical scavenging enzymes, such as superoxide dismutase or catalase. Additionally, the use of gene therapy approaches may significantly contribute to the development of strategies aimed at inhibiting of I/R injury.

Ischemia/Reperfusion Liver Reactive oxygen species Signal transduction Gene therapy NF-kB AP-1 Superoxide dismutase 

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • Chenguang Fan
    • 1
  • Ralf M. Zwacka
    • 2
  • John F. Engelhardt
    • 3
  1. 1.Molecular Biology Program, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242USA
  2. 2.Department of Oncology, University of Edinburgh, EdinburghUK
  3. 3.Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242USA
  4. 4.Department of Internal Medicine, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242USA

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