Botulinum Toxin Confers Radioprotection In Murine Salivary Glands

Department

Biomedical Sciences

Document Type

Abstract

Conference Title

American Society for Radiation Oncology, 55th Annual Meeting

Organization

American Society for Radiation Oncology

DOI

10.1016/j.ijrobp.2013.06.1691

Location

Atlanta, GA

Conference Dates

September 22-25, 2013

Date of Presentation

9-22-2013

Abstract

Purpose/Objectives: Xerostomia is a common radiation toxicity which negatively impacts the quality of life of HNC patients. Current treatment strategies offer partial relief at best. Besides their wide use in cosmetic procedures, botulinum toxins (BTX) have been successfully used in treating radiation sequelae as radiation-induced cystitis, proctitis, fibrosis and facial pain. The purpose of this study is to evaluate the effect of botulinum toxin on radiation-induced salivary gland damage.

Materials/Methods: We used a previously established model for murine salivary gland irradiation. Submandibular glands of C5BL6 mice (n = 6/group) were injected with saline or botulinum toxin 72 hrs prior to receiving 1500 cGy of focal gamma radiation. Saliva flow was measured at 3 and 7 days post treatment. Submandibular glands were collected at various time points for immunohistochemistry, confocal microscopy and Western blotting analysis. TUNEL staining was used to evaluate cell death. A cytokine array, consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment.

Results: Irradiated mice showed a 50% reduction in saliva flow whereas mice pre-injected with BTX had 25% reduction in saliva flow (p < 0.05) after 3 days. Cell death detected by TUNEL staining was similar in SMG sections from both groups. However, neutrophil infiltrate, detected via myeloperoxidase staining, was 2 to 3 fold lower for the BTX treated mice. A cytokine array showed 2 fold upregulation of LPS induced-chemokine (LIX/CXCL5), 3 days after irradiation. Interestingly, BTX pretreatment reduced LIX levels by 40%. At 4 weeks post irradiation, saline (control) group showed 40% reduction in basal SMG weight as compared to 20% in the BTX group. Histologically, BTX pretreated glands showed relative preservation of acinar volume post radiation.

Taken together, these data suggest that BTX pretreatment ameliorates radiation-induced salivary dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of radiation-induced salivary gland damage. These results carry important clinical implications for treatment of xerostomia in HNC patients.

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