title: Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis.
abstract: BACKGROUND
  The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 microg x 100 g(-1) x day(-1)). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage.
  
  
  METHODS
  Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry.
  
  
  RESULTS
  Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05).
  
  
  CONCLUSIONS
  the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.
authors.affiliation: Department of Physiology, School of Medicine, University of Navarra, Pamplona, Spain. igf@uma.es <igf@uma.es>
authors.forename: María
authors.initials: M
authors.lastname: García-Fernández
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla-Cortázar
authors.forename: Matías
authors.initials: M
authors.lastname: Díaz-Sanchez
authors.forename: Iñigo
authors.initials: I
authors.lastname: Navarro
authors.forename: Juan Enrique
authors.initials: JE
authors.lastname: Puche
authors.forename: Alberto
authors.initials: A
authors.lastname: Castilla
authors.forename: Amelia Díaz
authors.initials: AD
authors.lastname: Casares
authors.forename: Encarna
authors.initials: E
authors.lastname: Clavijo
authors.forename: Salvador
authors.initials: S
authors.lastname: González-Barón
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D014168:Transferrin; D008315:Malondialdehyde; D007334:Insulin-Like Growth Factor I; D003300:Copper; D005293:Ferritins; D007501:Iron
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