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Radiat Res. 2017 Jul;188(1):94-104. doi: 10.1667/RR14757.1.S1. Epub 2017 May 18.

Inhibition of the Continuum of Radiation-Induced Normal Tissue Injury by a Redox-Active Mn Porphyrin.

Author information

1
a   Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, 27710.
2
b   Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, 27710.
3
c   Department of Medicine, Duke University Medical Center, Durham, North Carolina, 27710.
4
d   Duke Cancer Institute, Pharmaceutical Research PK-PD Core Laboratory, Durham, North Carolina 27710.
5
e   Department of Medicine, National Jewish Health, Denver, Colorado 80206 and BioMimetix JV, LLC, Englewood, Colorado 80113.

Abstract

Normal tissue damage after head and neck radiotherapy involves a continuum of pathologic events to the mucosa, tongue and salivary glands. We examined the radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three stages of normal tissue damage: immediate (leukocyte endothelial cell [L/E] interactions), early (mucositis) and late (xerostomia and fibrosis) after treatment. In this study, mice received 0 or 9 Gy irradiation to the oral cavity and salivary glands ± MnBuOE treatment. Changes in leukocyte-endothelial cell interactions were measured 24 h postirradiation. At 11 days postirradiation, mucositis was assessed with a cathepsin-sensitive near-infrared optical probe. Stimulated saliva production was quantified at 11 weeks postirradiation. Finally, histological analyses were conducted to assess the extent of long-term effects in salivary glands at 12 weeks postirradiation. MnBuOE reduced oral mucositis, xerostomia and salivary gland fibrosis after irradiation. Additionally, although we have previously shown that MnBuOE does not interfere with tumor control at high doses when administered with radiation alone, most head and neck cancer patients will be treated with the combinations of radiotherapy and cisplatin. Therefore, we also evaluated whether MnBuOE would protect tumors against radiation and cisplatin using tumor growth delay as an endpoint. Using a range of radiation doses, we saw no evidence that MnBuOE protected tumors from radiation and cisplatin. We conclude that MnBuOE radioprotects normal tissue at both early and late time points, without compromising anti-tumor effects of radiation and cisplatin.

PMID:
28517962
PMCID:
PMC5559715
DOI:
10.1667/RR14757.1.S1
[Indexed for MEDLINE]
Free PMC Article

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