Liver
ischemia/reperfusion (I/R) injury, which is mainly caused by the generation of
reactive oxygen species (ROS) during the reperfusion, remains an important clinical problem associated with
liver transplantation and major liver surgery. Therefore, ROS should be detoxified to prevent hepatic I/R-induced injury. Delivery of
antioxidant genes into liver is considered to be promising for prevention of hepatic I/R injury; however,
therapeutic effects of
antioxidant gene transfer to the liver have not been fully examined. The aim of this study was to examine whether adenovirus (Ad) vector-mediated
catalase gene transfer in the liver is an effective approach for scavenging ROS and preventing hepatic I/R injury.
Intravenous administration of Ad vectors expressing
catalase, which is an
antioxidant enzyme scavenging H(2)O(2), resulted in a significant increase in
catalase activity in the liver. Pre-injection of
catalase-expressing Ad vectors dramatically prevented I/R-induced elevation in serum
alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) levels, and hepatic
necrosis. The livers were also protected in another liver injury model, CCl(4)-induced liver injury, by
catalase-expressing Ad vectors. Furthermore, the survival rates of mice subjected to both partial
hepatectomy and I/R treatment were improved by pre-injection of
catalase-expressing Ad vectors. On the other hand, control Ad vectors expressing
beta-galactosidase did not show any significant preventive effects in the liver on the models of I/R-induced or CCl(4)-induced hepatic injury described above. These results indicate that hepatic delivery of the
catalase gene by Ad vectors is a promising approach for the prevention of oxidative stress-induced liver injury.