Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury.
Publication/Presentation Date
10-1-2010
Abstract
BACKGROUND: Total parenteral nutrition (TPN) induced liver failure is the leading indication for transplantation in children. Our previous research demonstrated the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in the amelioration of TPN-induced liver injury. This study was designed to ascertain the optimum concentration of HGF in an animal model of TPN-induced liver injury.
MATERIALS AND METHODS: Twenty adult female Sprague-Dawley rats underwent 70% small bowel resection and placement of venous catheters connected to subcutaneous osmotic minipumps. Four groups (n=5 each) based on the contents of the osmotic pump were utilized as follows: group 1 (control): saline; group 2: HGF 75 mcg/kg/d; group 3: HGF 150 mcg/kg/d; and group 4: HGF 250 mcg/kg/d. Each rat received 14 d of TPN without enteral nutrition. After sacrifice, the liver was harvested. Hepatic inflammation was evaluated using antibodies for TNF-α and IL-6. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique.
RESULTS: All concentrations induced statistically significantly less IL-6 and TNF- α expression compared to the control animals. Increased efficacy was demonstrated with increasing dose concentration up to 150 mcg/kg/d but not 250 mcg/kg/d. Apoptotic activity was decreased statistically significantly for all dose concentrations compared with the controls, as well as to increases in dose concentration.
CONCLUSIONS: Increasing concentrations of HGF were directly correlated with increased modulation of inflammatory response and apoptotic index in this animal model for TPN-induced liver injury, up to 150 mcg/kg/d. Further increases were significant with respect to apoptotic index only. Further investigations are warranted to determine if HGF may be useful to minimize TPN-induced liver injury in children.
Volume
163
Issue
2
First Page
294
Last Page
298
ISSN
1095-8673
Published In/Presented At
Katz, M. S., Thatch, K. A., & Schwartz, M. Z. (2010). Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury. The Journal of surgical research, 163(2), 294–298. https://doi.org/10.1016/j.jss.2010.04.042
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
20691983
Department(s)
Department of Pediatrics, Department of Surgery
Document Type
Article