Cargando…

Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation

Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of...

Descripción completa

Detalles Bibliográficos
Autores principales: Gruber, Sylvia, Arnold, Marlene, Cini, Nilsu, Gernedl, Victoria, Hetzendorfer, Sabine, Kowald, Lisa-Marie, Kuess, Peter, Mayer, Julia, Morava, Susanne, Pfaffinger, Stephanie, Rohorzka, Andreas, Dörr, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032103/
https://www.ncbi.nlm.nih.gov/pubmed/29882770
http://dx.doi.org/10.3390/ijms19061684
_version_ 1783337440280313856
author Gruber, Sylvia
Arnold, Marlene
Cini, Nilsu
Gernedl, Victoria
Hetzendorfer, Sabine
Kowald, Lisa-Marie
Kuess, Peter
Mayer, Julia
Morava, Susanne
Pfaffinger, Stephanie
Rohorzka, Andreas
Dörr, Wolfgang
author_facet Gruber, Sylvia
Arnold, Marlene
Cini, Nilsu
Gernedl, Victoria
Hetzendorfer, Sabine
Kowald, Lisa-Marie
Kuess, Peter
Mayer, Julia
Morava, Susanne
Pfaffinger, Stephanie
Rohorzka, Andreas
Dörr, Wolfgang
author_sort Gruber, Sylvia
collection PubMed
description Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation.
format Online
Article
Text
id pubmed-6032103
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-60321032018-07-13 Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation Gruber, Sylvia Arnold, Marlene Cini, Nilsu Gernedl, Victoria Hetzendorfer, Sabine Kowald, Lisa-Marie Kuess, Peter Mayer, Julia Morava, Susanne Pfaffinger, Stephanie Rohorzka, Andreas Dörr, Wolfgang Int J Mol Sci Article Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation. MDPI 2018-06-06 /pmc/articles/PMC6032103/ /pubmed/29882770 http://dx.doi.org/10.3390/ijms19061684 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gruber, Sylvia
Arnold, Marlene
Cini, Nilsu
Gernedl, Victoria
Hetzendorfer, Sabine
Kowald, Lisa-Marie
Kuess, Peter
Mayer, Julia
Morava, Susanne
Pfaffinger, Stephanie
Rohorzka, Andreas
Dörr, Wolfgang
Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title_full Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title_fullStr Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title_full_unstemmed Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title_short Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation
title_sort radioprotective effects of dermatan sulfate in a preclinical model of oral mucositis—targeting inflammation, hypoxia and junction proteins without stimulating proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032103/
https://www.ncbi.nlm.nih.gov/pubmed/29882770
http://dx.doi.org/10.3390/ijms19061684
work_keys_str_mv AT grubersylvia radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT arnoldmarlene radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT cininilsu radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT gernedlvictoria radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT hetzendorfersabine radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT kowaldlisamarie radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT kuesspeter radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT mayerjulia radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT moravasusanne radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT pfaffingerstephanie radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT rohorzkaandreas radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation
AT dorrwolfgang radioprotectiveeffectsofdermatansulfateinapreclinicalmodeloforalmucositistargetinginflammationhypoxiaandjunctionproteinswithoutstimulatingproliferation