ADENO ASSOCIATED VIRAL GENE DELIVERY AND OXIDATIVE STRES

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Alcohol-induced liver injury can be attributed largely to oxidative stress, most likely due to ischemia/reperfusion injury; however, the exact mechanisms involved are still unknown. Additionally, alcohol is associated with a decrease in anti- oxidant protection; therefore, it is hypothesized that delivery of antioxidant enzymes superoxide dismutase (SOD) and catalase via recombinant adeno-associated virus (rAAV) will be protective against oxidative stress. To test this hypothesis, SOD and catalase will be delivered via adenovirus and adeno-associated virus and will be assessed for protection against oxidative injury in ischemia/reperfusion models as well as in the clinically relevant Tsukamoto-French enteral feeding model of alcoholic liver disease. Furthermore, oxidative stress has been suggested to increase rAAV transduction in vitro. Therefore, we will test the hypothesis that oxidative stress caused by chronic ethanol will increase rAAV transduction in vivo. Because alcohol-induced liver disease is a prevalent, devastating disease, it is the objective of this work to gain new insight into the mechanism of alcohol-induced liver injury, and to provide exciting new approaches for clinical application.