Impact of Age on Liver Regeneration Response to Injury After Partial Hepatectomy in a Rat Model

• Published in: The Journal of surgical research 2012-06, Vol.175 (1), p.e1-e9
• Main Authors: Sánchez-Hidalgo, Juan Manuel, M.D., Ph.D, Naranjo, Álvaro, M.D, Ciria, Rubén, M.D., Ph.D, Ranchal, Isidora, Ph.D, Aguilar-Melero, Patricia, Ph.D, Ferrín, Gustavo, Ph.D, Valverde, Amparo, M.D, Rufián, Sebastián, M.D., Ph.D, López-Cillero, Pedro, M.D., Ph.D, Muntané, Jordi, Ph.D, Briceño, Javier, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: aged; Animals; Hepatectomy - mortality; HGF; IL-6; Liver - pathology; Liver - physiology; Liver Regeneration - physiology; liver resection; Male; nitric oxide; oxidative stress; proliferation; Rats; Rats, Wistar; regeneration; Surgery; TGF-β; TNF-α
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2011.11.1022

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. Conclusion Liver regeneration is delayed and reduced in aged animals submitted to liver resection.