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Int. J. Mol. Sci. 2018, 19(6), 1684; https://doi.org/10.3390/ijms19061684

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

1
Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University/AKH Vienna, 1090 Vienna, Austria
2
Department of Radiation Oncology, Applied and Translational Radiobiology, Medical University Vienna, 1090 Vienna, Austria
3
Department of Radiation Oncology, Kartal Dr. Lutfi Kırdar Training and Research Hospital, Health Science University, 34722 Istanbul, Turkey
*
Author to whom correspondence should be addressed.
Received: 11 May 2018 / Revised: 23 May 2018 / Accepted: 23 May 2018 / Published: 6 June 2018
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research)
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Abstract

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. View Full-Text
Keywords: oral mucositis; mouse model; dermatan sulfate; fractionation; inflammation; hypoxia; cellular junctions oral mucositis; mouse model; dermatan sulfate; fractionation; inflammation; hypoxia; cellular junctions
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Gruber, S.; Arnold, M.; Cini, N.; Gernedl, V.; Hetzendorfer, S.; Kowald, L.-M.; Kuess, P.; Mayer, J.; Morava, S.; Pfaffinger, S.; Rohorzka, A.; Dörr, W. Radioprotective Effects of Dermatan Sulfate in a Preclinical Model of Oral Mucositis—Targeting Inflammation, Hypoxia and Junction Proteins without Stimulating Proliferation. Int. J. Mol. Sci. 2018, 19, 1684.

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