Radioprotective effects of amifostine on acute and chronic esophageal injury in rodents.

Published

Journal Article

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 integrinalphavbeta6 and transforming growth factor (TGF)-beta were performed 5 days and 10 weeks after irradiation. RESULTS: Pre-RT mean mucosal thickness was 35 microm in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 microm in the placebo group versus 37 microm 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 integrinalphavbeta6 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 integrinalphavbeta6 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.

Full Text

Duke Authors

Cited Authors

  • Vujaskovic, Z; Thrasher, BA; Jackson, IL; Brizel, MB; Brizel, DM

Published Date

  • October 1, 2007

Published In

Volume / Issue

  • 69 / 2

Start / End Page

  • 534 - 540

PubMed ID

  • 17869666

Pubmed Central ID

  • 17869666

International Standard Serial Number (ISSN)

  • 0360-3016

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2007.05.062

Language

  • eng

Conference Location

  • United States