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

Jian Wu, Li Liu, Roy D. Yen, Andreea Catana, Michael H. Nantz, Mark A Zern

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Our previous study demonstrated that polycationic liposomes are highly stable in the blood-stream 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 showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. In conclusion, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity in vitro and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice.

Original languageEnglish (US)
Pages (from-to)195-204
Number of pages10
JournalHepatology
Volume40
Issue number1
DOIs
StatePublished - Jul 2004

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Liposomes
Superoxide Dismutase
Liver
Wounds and Injuries
Genes
Galactosamine
Hep G2 Cells
Lipopolysaccharides
Reactive Oxygen Species
Plasmids
Cell Death
Portal Vein
Reverse Transcriptase Polymerase Chain Reaction
Serum
Alanine Transaminase
Superoxides
Lipid Peroxidation
Transfection
Glutathione
Histology

ASJC Scopus subject areas

  • Hepatology

Cite this

Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice. / Wu, Jian; Liu, Li; Yen, Roy D.; Catana, Andreea; Nantz, Michael H.; Zern, Mark A.

In: Hepatology, Vol. 40, No. 1, 07.2004, p. 195-204.

Research output: Contribution to journalArticle

Wu, Jian ; Liu, Li ; Yen, Roy D. ; Catana, Andreea ; Nantz, Michael H. ; Zern, Mark A. / Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice. In: Hepatology. 2004 ; Vol. 40, No. 1. pp. 195-204.
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