Radioprotective Effects of Amifostine on Acute and Chronic Esophageal Injury in Rodents

Journal Article · Mon Oct 01 04:00:00 EDT 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2007.05.062· OSTI ID:21036258

Vujaskovic, Zeljko; Thrasher, Bradley A; Jackson, Isabel L; Brizel, Marla B ^[1]

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1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

Purpose: This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model. Methods: Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrin{alpha}v{beta}6 and transforming growth factor (TGF)-{beta} were performed 5 days and 10 weeks after irradiation. Results: Pre-RT mean mucosal thickness was 35 {mu}m in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 {mu}m in the placebo group versus 37 {mu}m in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-{beta}, and integrin{alpha}v{beta}6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group. Conclusions: This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrin{alpha}v{beta}6 expression which reduces TGF-{beta} activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings.

• OSTI ID: 21036258
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 69; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
COLLAGEN
EPITHELIUM
ESOPHAGUS
GROWTH FACTORS
INJURIES
INTRAPERITONEAL INJECTION
IRRADIATION
MACROPHAGES
OXIDATION
RADIOPROTECTIVE SUBSTANCES
RATS
THICKNESS
X RADIATION