Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY (United States)
- Second Military Medical College, Shanghai (China)
- Brookhaven National Laboratory, Medical Department, Upton, NY (United States)
- Department of Surgery, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian (China)
- Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan (China)
- Department of Medicine, University of Rochester Medical Center, Rochester, NY (United States)
Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. Methods and Materials: A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Results: Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. Conclusions: The study data support pursuing FGF-P as a mitigator for AGS.
- OSTI ID:
- 21372268
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 77, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2009.11.026; PII: S0360-3016(09)03567-6; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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LYMPHOKINES
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