title: Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine.
abstract: BACKGROUND
  A mouse model in which N-diethylnitrosamine (DEN) induces Hepatocellular carcinoma (HCC) has histological and genetic resemblance to human tumours.
  
  
  METHODS
  Male ICR mice were divided into control (n=10) and DEN-treated (n=10) groups. DEN was administered via intraperitoneal injection, once a week, for eight consecutive weeks. Animals were euthanized seven weeks after the last administration of DEN and their livers were collected. Plasma albumin, total bilirubin, alanine transaminase and aspartate aminotransferase activity were all measured and liver mitochondrial bioenergetics and oxidative stress were also evaluated.
  
  
  RESULTS
  Histologically, pre-neoplastic lesions were identified in the livers of mice from the DEN group. Total plasma bilirubin increased significantly in the group exposed to DEN and mitochondrial complex I and IV were significantly inhibited (p=0.0403 and p=0.0053, respectively).
  
  
  CONCLUSIONS
  DEN induced changes in liver bioenergetics and antioxidant capacity towards reactive oxygen species, seven weeks after administration. At this stage, liver tissues in mice exposed to DEN still had the ability to counteract the oxidative effects of DEN by increasing the activity of antioxidant enzymes.
authors.affiliation: Veterinary and Animal Science Research Centre, Department of Veterinary Science, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Nuno Paula
authors.initials: NP
authors.lastname: Santos
authors.forename: Ivo Conceição
authors.initials: IC
authors.lastname: Pereira
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pires
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Rita
authors.initials: R
authors.lastname: Andrade
authors.forename: Maria Manuel
authors.initials: MM
authors.lastname: Oliveira
authors.forename: Aura
authors.initials: A
authors.lastname: Colaço
authors.forename: Francisco
authors.initials: F
authors.lastname: Peixoto
authors.forename: Paula Alexandra
authors.initials: PA
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002273:Carcinogens / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D004052:Diethylnitrosamine / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D017382:Reactive Oxygen Species; D004052:Diethylnitrosamine