Research

Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis

Lynne A Murray^1*, Michael S Kramer¹, David P Hesson¹, Brynmor A Watkins², Edward G Fey², Rochelle L Argentieri¹, Furquan Shaheen³, Darryl A Knight³ and Stephen T Sonis^4,2

• * Corresponding author: Lynne A Murray murrayl@medimmune.com

Author Affiliations

¹ Promedior, Inc, 371 Phoenixville Pike, Malvern, PA, 19355, USA

² Biomodels and Affiliates, 313 Pleasant Street, Watertown, MA, 02472, USA

³ Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Burrard Street, Vancouver, Canada

⁴ Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine Diviosn of Oral Medicine, Dana Farber Cancer Institute, Brigham And Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA

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Fibrogenesis & Tissue Repair 2010, 3:11 doi:10.1186/1755-1536-3-11

Published: 5 July 2010

Abstract

Purpose

To evaluate the effect of the anti-fibrotic protein serum amyloid P (SAP) on radiation-induced oral mucositis (OM) and fibrosis in a hamster cheek-pouch model.

Experimental Design

Hamsters received a single dose of radiation (40 Gy) to the left everted cheek pouch to induce significant OM. The protective therapeutic potential of SAP was evaluated using varying dosing regimens. The extent of OM was measured using a validated six-point scoring scheme ranging from 0 (normal tissue, no mucositis) to 5 (complete ulceration). Fibrotic remodeling was also visualized histologically and quantified at later time points using collagen gene expression.

Results

SAP treatment attenuated the profile of radiation-induced oral mucositis by delaying the time of onset, reducing the peak value, and enhancing the resolution of injury. The peak mucositis score was reduced by approximately 0.5 grade in SAP-treated animals. The number of animal days with a score of ≥ 3 was reduced by 48% in the SAP-treated group, compared with the saline control group (P < 0.01). SAP also inhibited the extent of tissue remodeling and decreased radiation-induced increases in myofibroblast number. Attenuated collagen deposition and gene expression was also observed in the cheek pouches of hamsters treated with SAP at both 16 and 28 days post-radiation.

Conclusions

SAP treatment significantly attenuated radiation-induced injury. In particular, SAP attenuated the severity of OM and inhibited pathogenic remodeling. This suggests that SAP may be a useful therapy for the palliation of side effects observed during treatment for head and neck cancer.