title: EC-SOD gene therapy reduces paracetamol-induced liver damage in mice.
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 x 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
authors.forename: M O
authors.initials: MO
authors.lastname: Laukkanen
authors.forename: P
authors.initials: P
authors.lastname: Leppanen
authors.forename: P
authors.initials: P
authors.lastname: Turunen
authors.forename: T
authors.initials: T
authors.lastname: Tuomisto
authors.forename: J
authors.initials: J
authors.lastname: Naarala
authors.forename: S
authors.initials: S
authors.lastname: Yla-Herttuala
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006520:Hepatitis, Animal / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D000082:Acetaminophen; D013482:Superoxide Dismutase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases