EC-SOD gene therapy reduces paracetamol-induced liver damage in mice

Mikko O. Laukkanen, Pia Leppanen, Paivi Turunen, Tiina Tuomisto, Jonne Naarala, Seppo Yla-Herttuala

Research output: Contribution to journalArticle

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 ×109 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.

Original languageEnglish
Pages (from-to)321-325
Number of pages5
JournalJournal of Gene Medicine
Volume3
Issue number4
DOIs
Publication statusPublished - Jul 2001

Keywords

  • Apoptosis
  • Extracellular superoxide dismutase (EC-SOD)
  • Gene transfer
  • Inflammation
  • N-acetyl-p-aminophenol (acetaminophen, APAP)
  • Necrosis

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Laukkanen, M. O., Leppanen, P., Turunen, P., Tuomisto, T., Naarala, J., & Yla-Herttuala, S. (2001). EC-SOD gene therapy reduces paracetamol-induced liver damage in mice. Journal of Gene Medicine, 3(4), 321-325. https://doi.org/10.1002/jgm.194