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Title: Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

Abstract

Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicinmore » treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.« less

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR (United States)
  2. Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR (United States) and Department of Pathology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR (United States). E-mail: mhjensen@life.uams.edu
Publication Date:
OSTI Identifier:
20793440
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.12.035; PII: S0360-3016(06)00082-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ABLATION; CALCITONIN; COLLAGEN; CRYPT CELLS; FIBROSIS; GROWTH FACTORS; MAST CELLS; NERVE CELLS; NERVES; RADIATION INJURIES; RATS; SMALL INTESTINE; TOXICITY

Citation Formats

Wang Junru, Zheng Huaien, Kulkarni, Ashwini, Ou Xuemei, and Hauer-Jensen, Martin. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Wang Junru, Zheng Huaien, Kulkarni, Ashwini, Ou Xuemei, & Hauer-Jensen, Martin. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves. United States. doi:10.1016/J.IJROBP.2005.1.
Wang Junru, Zheng Huaien, Kulkarni, Ashwini, Ou Xuemei, and Hauer-Jensen, Martin. Sat . "Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793440,
title = {Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves},
author = {Wang Junru and Zheng Huaien and Kulkarni, Ashwini and Ou Xuemei and Hauer-Jensen, Martin},
abstractNote = {Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 64,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 2006},
month = {Sat Apr 01 00:00:00 EST 2006}
}