Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

• Published in: International journal of radiation oncology, biology, physics Vol. 77; no. 1; pp. 261 - 268
• Main Authors: Zhang, Lurong, M.D., Ph.D, Sun, Weimin, M.D, Wang, Jianjun, M.D, Zhang, Mei, M.D, Yang, Shanmin, M.D, Tian, Yeping, M.D., Ph.D, Vidyasagar, Sadasivan, M.D., Ph.D, Peña, Louis A., Ph.D, Zhang, Kunzhong, Ph.D, Cao, Yongbing, M.D., Ph.D, Yin, Liangjie, M.Sc, Wang, Wei, M.D., Ph.D, Zhang, Lei, M.D, Schaefer, Katherine L., Ph.D, Saubermann, Lawrence J., M.D, Swarts, Steven G., Ph.D, Fenton, Bruce M., Ph.D, Keng, Peter C., Ph.D, Okunieff, Paul, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2010; Elsevier
• Subjects: AGS; AMYLASE; ANIMAL CELLS; ANIMALS; AROMATICS; Biological and medical sciences; BIOLOGICAL MATERIALS; Biomarkers - blood; BLOOD; BLOOD CELLS; Blood Glucose - drug effects; BODY FLUIDS; Bone Marrow - drug effects; Bone Marrow - radiation effects; CELL PROLIFERATION; Chemokine CCL2 - blood; Chemokines - blood; CONNECTIVE TISSUE CELLS; CRYPT CELLS; DIGESTIVE SYSTEM; Drug Evaluation, Preclinical - methods; DYES; Endotoxemia - etiology; Endotoxemia - prevention & control; ENZYMES; FGF2 peptide; Fibroblast Growth Factor 2 - therapeutic use; FIBROBLASTS; GASTROINTESTINAL TRACT; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - radiation effects; GI function; GLYCOSYL HYDROLASES; GROWTH FACTORS; Hematology, Oncology and Palliative Medicine; HEMATOXYLIN; HETEROCYCLIC COMPOUNDS; HETEROCYCLIC OXYGEN COMPOUNDS; HORMONES; HYDROLASES; HYDROXY COMPOUNDS; INJECTION; INSULIN; Insulin - blood; INTAKE; Interleukin-6 - blood; INTRAMUSCULAR INJECTION; IONIZING RADIATIONS; LEUKOCYTES; LYMPHOKINES; Male; MAMMALS; MATERIALS; Medical sciences; MICE; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; MITIGATION; MITOGENS; MONOCYTES; O-GLYCOSYL HYDROLASES; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; Peptide Fragments - therapeutic use; PEPTIDE HORMONES; PEPTIDES; Pharmacology. Drug treatments; PHENOLS; POLYPHENOLS; PROTEINS; PYRANS; Radiation Injuries, Experimental - blood; Radiation Injuries, Experimental - mortality; Radiation Injuries, Experimental - prevention & control; Radiation-Protective Agents - therapeutic use; RADIATIONS; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RODENTS; SOMATIC CELLS; Species Specificity; Subtotal body irradiation; Syndrome; Tumor Necrosis Factor-alpha - blood; VERTEBRATES; Mitigation; GI function; FGF2 peptide; AGS; Subtotal body irradiation; Total body irradiation; Radioprotector; Rodentia; Basic fibroblast growth factor; Intramuscular administration; Vertebrata; Ionizing radiation; Mammalia; Mouse; Animal; Gastrointestinal diseases; Radiation injury; Complication; High dose
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2009.11.026

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)–α 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-α), FGF-P reduced these adverse responses. Conclusions The study data support pursuing FGF-P as a mitigator for AGS.