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J Surg Res. 2012 Jun 1;175(1):e1-9. doi: 10.1016/j.jss.2011.11.1022. Epub 2011 Dec 14.

Impact of age on liver regeneration response to injury after partial hepatectomy in a rat model.

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1
Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofia, Córdoba, Spain.

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.

CONCLUSION:

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

PMID:
22341343
DOI:
10.1016/j.jss.2011.11.1022
[Indexed for MEDLINE]
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