A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide

Abstract

Purpose: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development.

Materials and methods: Hamsters’ cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1β and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively.

Results: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1β and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production.

Conclusion: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1β and NO seem to play a role in the pathophysiology of this model.

Keywords::

• Megavoltage radiation
• oral mucositis
• animal model
• nitric oxide
• tumor necrosis factor-α
• interleukin-1β

Acknowledgements

We are grateful to Mrs Maria Silvandira Freire and Mr José Ivan Rodrigues for their technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Fundação Cearense de Apoio a Pesquisa (FUNCAP, Brazil) through Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil) and Núcleo de Estudos da Toxicidade do Tratamento Oncológico (NETTO, Brazil).

Supplementary material available online

Supplementary Figure 1 and Table I.