title: Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats.
abstract: BACKGROUND
  GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats.
  
  
  METHODS
  Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight⁻¹ * day⁻¹) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method.
  
  
  RESULTS
  Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations.
  
  
  CONCLUSIONS
  We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.
authors: Department of Medical Physiology, CEU-San Pablo University School of Medicine Institute of Applied Molecular Medicine (IMMA) Boadilla del Monte, 28668 Madrid, Spain. iccortazar@ceu.es
authors: Inma
authors: I
authors: Castilla-Cortázar
authors: María
authors: M
authors: García-Fernández
authors: Gloria
authors: G
authors: Delgado
authors: Juan E
authors: JE
authors: Puche
authors: Inma
authors: I
authors: Sierra
authors: Rima
authors: R
authors: Barhoum
authors: Salvador
authors: S
authors: González-Barón
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000008:administration & dosage* / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
chemical_list: D000975:Antioxidants; D006728:Hormones; D007328:Insulin; D020011:Protective Agents; D013739:Testosterone; D008315:Malondialdehyde; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005947:Glucose