Journal article
Growth factor modulation of hepatic inflammation: a novel approach to the management of total parenteral nutrition-associated liver disease
Journal of pediatric surgery, v 45(1), pp 89-94
01 Jan 2010
PMID: 20105586
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose: Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model.
Methods: Female Sprague-Dawley rats were divided into 3 groups: control (n = 5), chronic liver injury (alpha-naphtylisocyocyanate [ANIT] every 3.5 days at 75 mg/kg; n = 5), and chronic liver injury plus HGF (ANIT + HGF at 250 mu g kg(-1) d(-1); n = 5). The rats initially underwent massive (80%) small bowel resections. Seven days later, they were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic minipump for continuous intravenous saline or HGF. Intraperitoneal saline or ANIT injections were subsequently administered every 3.5 days to create a chronic cholestatic model. After 14 days, the animals were euthanized, and liver biopsies were obtained. The liver biopsies were evaluated by histology, immunofluorescence staining for interleukin-6 and tumor necrosis factor a, and assessment of apoptosis by terminal dUTP-transferase-mediated nick end labeling (TUNEL) technique.
Results: In this chronic liver injury model, HGF did not effect the grade of inflammation. However, HGF did induce retention of the ductal structures and avoided ductal proliferation, damage, and evidence of primary sclerosing cholangitis (P < .05). Hepatocyte growth factor induced less interleukin-6 (P < .011) and tumor necrosis factor a (P < .01) expression. Apoptotic activity was also significantly less in the HGF group (P < .01).
Conclusion: Hepatocyte growth factor preserved the hepatic ductal system, modulated the hepatic inflammatory response, and reduced the apoptotic index in this chronic cholestatic liver injury model. It may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury. (C) 2010 Elsevier Inc. All rights reserved.
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Details
- Title
- Growth factor modulation of hepatic inflammation: a novel approach to the management of total parenteral nutrition-associated liver disease
- Creators
- Keith A. Thatch - St. Christopher's Hospital for ChildrenMichael S. Katz - St. Christopher's Hospital for ChildrenMarian M. Haber - Drexel UniversityMarshall Z. Schwartz - Drexel University
- Publication Details
- Journal of pediatric surgery, v 45(1), pp 89-94
- Publisher
- Elsevier
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000274393800014
- Scopus ID
- 2-s2.0-72649085709
- Other Identifier
- 991019168487104721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Pediatrics
- Surgery