Mechanism of action of benzydamine in the treatment of oral mucositis

Abstract

8040 Background: BZD has been proposed as a topical intervention for radiation-induced (RT) OM. BZD has been reported to have a range of biological activities that intervere with many of the mechanisms that are thought to be of importance in the pathogenesis of RT-induced OM. The objective of this study was to define the mechanisms by which BZD attenuates RT-induced OM. Methods: The effect of topically applied BZD on selected morphological and biological parameters was studied in temporal fashion to develop a descriptive pattern of events from which suggestions of mechanisms could be derived. 60 golden Syrian hamsters were randomized into 3 groups (G1 placebo n=32, G2 BZD n=32, G3 no treatment n=4). G1 and G2 animals were treated qd on day (d) 0 (day of RT) and then qid for 28d by injection into the left buccal cheek pouch. A single 37Gy radiation dose was administered to the left buccal pouch of all animals on d0. Four animals from G1 and G2 were sacrificed on d1,4,8,12,16,18 and 28, their left buccal pouches removed and the tissue studies for a variety of histological and immunohistochemical outcomes and markers. Results: Topical application of 0.15% BZD resulted in macroscopic attenuation of OM. A biphasic response characterized many study endpoints. Histological outcomes reflected tissue injury. BZD modified epithelial proliferation, but not differentiation. Observed changes correlated with a reduction in tissue levels of interleukin (IL)-1beta and tumor necrosis factor-alpha, but not IL-6. Preferential antiapoptotic activity was seen in epithelium and connective tissue of BZD-treated animals. Endothelial expression of COX-2 was altered by BZD. Conclusions: BZD’s effect in this model correlated with its selective attenuation of pro-inflammatory cytokines and its modification of epithelial and connective tissue apoptosis. These data do not indicate whether these effects are mechanistic drivers of OM or downstream markers of a more fundamental biological effect. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration McNeil Consumer and Specialty Pharmaceuticals Biomodels LLC, McNeil