Liver transplantation is the only therapeutic strategy for many inherited and acquired diseases. The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial superoxide dismutase gene transfer to the liver for acute ischemia/reperfusion injury. Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse liver prior to lobar ischemia/reperfusion significantly reduced acute liver damage and associated redox activation of both NF-κB and AP1. These immediate early transcription factors represent common pathways by which cells respond to environmental stress. This work provides the foundation for redox-mediated gene therapies directed at ameliorating ischemia/reperfusion injury and associated acute rejection in orthotopic liver transplantation.
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Zwacka, R., Zhou, W., Zhang, Y. et al. Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-κB activation. Nat Med 4, 698–704 (1998) doi:10.1038/nm0698-698
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