Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia...

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Veröffentlicht in:Journal of dental research Jg. 97; H. 11; S. 1252
Hauptverfasser: Varghese, J J, Schmale, I L, Mickelsen, D, Hansen, M E, Newlands, S D, Benoit, D S W, Korshunov, V A, Ovitt, C E
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.10.2018
Schlagworte:
Acinar Cells - drug effects
Acinar Cells - radiation effects
Amifostine - administration & dosage
Amifostine - therapeutic use
Animals
Female
Fluorescent Antibody Technique
Injections
Mercaptoethylamines - administration & dosage
Mercaptoethylamines - therapeutic use
Mice
Mice, Inbred C57BL
Radiation Injuries, Experimental - pathology
Radiation Injuries, Experimental - prevention & control
Radiation-Protective Agents - administration & dosage
Radiation-Protective Agents - therapeutic use
Salivary Glands - drug effects
Salivary Glands - pathology
Salivary Glands - radiation effects
Submandibular Gland - drug effects
Submandibular Gland - radiation effects
hypotension
saliva
acinar cells
submandibular gland
radiation
salivary ducts
ISSN:1544-0591, 1544-0591
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Zusammenfassung:Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1544-0591
1544-0591
DOI:10.1177/0022034518767408