Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Jian WuMark A Zern

Abstract

Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction sho...Continue Reading

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