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Tytuł pozycji:

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

Tytuł :
Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis-Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation.
Autorzy :
Gruber S; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University/AKH Vienna, 1090 Vienna, Austria. .; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Arnold M; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Cini N; Department of Radiation Oncology, Kartal Dr. Lutfi Kırdar Training and Research Hospital, Health Science University, 34722 Istanbul, Turkey. .
Gernedl V; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Hetzendorfer S; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Kowald LM; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Kuess P; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University/AKH Vienna, 1090 Vienna, Austria. .
Mayer J; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Morava S; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Pfaffinger S; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Rohorzka A; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
Dörr W; Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria. .
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Źródło :
International journal of molecular sciences [Int J Mol Sci] 2018 Jun 06; Vol. 19 (6). Date of Electronic Publication: 2018 Jun 06.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms :
Dermatan Sulfate/*therapeutic use
Head and Neck Neoplasms/*radiotherapy
Radiation-Protective Agents/*therapeutic use
Radiotherapy/*adverse effects
Stomatitis/*drug therapy
Stomatitis/*etiology
Animals ; Cell Proliferation/drug effects ; Disease Models, Animal ; Hypoxia/drug therapy ; Hypoxia/etiology ; Hypoxia/pathology ; Inflammation/drug therapy ; Inflammation/etiology ; Inflammation/pathology ; Intercellular Junctions/drug effects ; Intercellular Junctions/pathology ; Mice ; Stomatitis/pathology
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Contributed Indexing :
Keywords: cellular junctions*; dermatan sulfate*; fractionation*; hypoxia*; inflammation*; mouse model*; oral mucositis*
Substance Nomenclature :
0 (Radiation-Protective Agents)
24967-94-0 (Dermatan Sulfate)
Entry Date(s) :
Date Created: 20180609 Date Completed: 20181015 Latest Revision: 20190808
Update Code :
20210623
PubMed Central ID :
PMC6032103
DOI :
10.3390/ijms19061684
PMID :
29882770
Czasopismo naukowe
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.
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