title: Impact of age on liver regeneration response to injury after partial hepatectomy in a rat model.
abstract: BACKGROUND
  Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration.
  
  
  OBJECTIVE
  To assess the effect of age on liver regeneration in an experimental in vivo animal model of 70%-partial hepatectomy.
  
  
  METHODS
  Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined.
  
  
  RESULTS
  Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- α) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-β were higher in young rats.
  
  
  CONCLUSIONS
  Liver regeneration is delayed and reduced in aged animals submitted to liver resection.
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, Córdoba, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sánchez-Hidalgo
authors.forename: Alvaro
authors.initials: A
authors.lastname: Naranjo
authors.forename: Rubén
authors.initials: R
authors.lastname: Ciria
authors.forename: Isidora
authors.initials: I
authors.lastname: Ranchal
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Melero
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ferrín
authors.forename: Amparo
authors.initials: A
authors.lastname: Valverde
authors.forename: Sebastián
authors.initials: S
authors.lastname: Rufián
authors.forename: Pedro
authors.initials: P
authors.lastname: López-Cillero
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
authors.forename: Javier
authors.initials: J
authors.lastname: Briceño
mesh_terms: D000818:Animals; D006498:Hepatectomy / Q000401:mortality*; D008099:Liver / Q000473:pathology / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar