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EC‐SOD gene therapy reduces paracetamol‐induced liver damage in mice
Author(s) -
Laukkanen Mikko O.,
Leppanen Pia,
Turunen Paivi,
Tuomisto Tiina,
Naarala Jonne,
YlaHerttuala Seppo
Publication year - 2001
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.194
Subject(s) - superoxide dismutase , superoxide , pharmacology , oxidative stress , acetaminophen , chemistry , extracellular , necrosis , reactive oxygen species , enzyme , microbiology and biotechnology , biochemistry , medicine , pathology , biology
Abstract Background Paracetamol overdose causes acute liver damage which leads to severe centrilobular hepatic necrosis. The hepatotoxic effect is caused by reactive metabolites and oxidative stress. Since extracellular superoxide dismutase (EC‐SOD) protects tissues against the harmful effects of superoxide anion, the hypothesis that systemic adenovirus‐mediated EC‐SOD gene transfer could reduce liver damage was tested. Methods Mice were given paracetamol (600 mg/kg) enterally 2 days after adenovirus‐mediated gene transfer of EC‐SOD (2×10 9 pfu). Five days after gene transfer, plasma and tissue samples were collected for clinical chemistry analyses and tissue pathology evaluation. Results EC‐SOD was expressed in a dose‐dependent manner with the highest enzyme activity occurring 3 days after the gene transfer. Clinical chemistry and tissue pathology analyses showed that adenoviral EC‐SOD gene transfer significantly attenuated release of liver enzymes and inhibited necrosis and apoptosis caused by paracetamol overdose. Conclusion The results indicate the involvement of superoxide anion in paracetamol‐mediated liver damage and suggest a possible protective role for EC‐SOD gene transfer in paracetamol‐induced liver damage. Copyright © 2001 John Wiley & Sons, Ltd.