Lentivirus-mediated superoxide dismutase1 gene delivery protects against oxidative stress-induced liver injury in mice
Version of Record online: 20 NOV 2007
Volume 27, Issue 10, pages 1311–1322, December 2007
How to Cite
Venugopal, S. K., Wu, J., Catana, A. M., Eisenbud, L., He, S.-Q., Duan, Y.-Y., Follenzi, A. and Zern, M. A. (2007), Lentivirus-mediated superoxide dismutase1 gene delivery protects against oxidative stress-induced liver injury in mice. Liver International, 27: 1311–1322. doi: 10.1111/j.1478-3231.2007.01612.x
- Issue online: 20 NOV 2007
- Version of Record online: 20 NOV 2007
- Received 6 February 2007accepted 27 August 2007
- gene therapy;
- liver injury;
- oxidative stress;
Background: The exposure of liver to hepatotoxins, and their subsequent metabolism, results in increased reactive oxygen species (ROS), one of the major culprits in causing both acute liver cell injury and chronic liver diseases. The aim of this present study is to investigate the protective effects of lentiviral vector-mediated copper–zinc superoxide dismutase (LV-SOD1) gene transfer against ROS-induced cytotoxicity in Hep G2 cells and liver injury in mice.
Methods: In vitro SOD1 efficacy was tested against two ROS-generating systems: hypoxanthine/xanthine oxidase (HX/XO) and hydroxyethyl radicals (HER), whereas in vivo SOD1 efficacy was evaluated in carbon tetrachloride (CCl4)-induced liver injury in C57BL/6 mice.
Results: LV-SOD1 transduction in Hep G2 cells resulted in a significant increase in SOD activity in cell lysates, and it significantly decreased the toxicity induced by HX/XO and HER. High SOD1 expression in the liver was achieved via portal vein injection of LV-SOD1 in mice and these high levels were observed for 30 days, the length of the experiment to date. SOD1 overexpression significantly decreased the toxicity and restored liver function in the CCl4-treated mice.
Conclusions: These findings demonstrate for the first time that LV transduction led to the long-term expression of fully functional transgene expression in both in vitro and in vivo systems.