title: Mitochondrial protection by low doses of insulin-like growth factor- I in experimental cirrhosis.
abstract: OBJECTIVE
  To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I (IGF- I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection.
  
  
  METHODS
  Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF- I treatment (2 microg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups.
  
  
  RESULTS
  Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF- I therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes I and III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- I therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis.
  
  
  CONCLUSIONS
  These results show that IGF- I exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.
authors.affiliation: Department of Human Physiology and Internal Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Pérez
authors.forename: María
authors.initials: M
authors.lastname: García-Fernández
authors.forename: Matías
authors.initials: M
authors.lastname: Díaz-Sánchez
authors.forename: Juan E
authors.initials: JE
authors.lastname: Puche
authors.forename: Gloria
authors.initials: G
authors.lastname: Delgado
authors.forename: Marian
authors.initials: M
authors.lastname: Conchillo
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla-Cortázar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D045222:Electron Transport Chain Complex Proteins; D005609:Free Radicals; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D002251:Carbon Tetrachloride; C505410:Casp3 protein, rat; D053148:Caspase 3; D025261:Mitochondrial Proton-Translocating ATPases