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

作者：Bastos Moura Jose Fernando; Segundo Correia Mota Jose Mauricio; Vitorino Leite Caio Abner; Wong Deysi Viviana T; Bezerra Nilfacio Prado; De Castro Brito Gerly Anne; Lima Vilma; Cunha Fernando Queiroz; Ribeiro Ronaldo Albuquerque^*

来源：International Journal of Radiation Biology, 2015, 91(6): 500-509.

DOI：10.3109/09553002.2015.1021964

• Megavoltage radiation
• oral mucositis
• animal model
• nitric oxide
• tumor necrosis factor-alpha
• interleukin-1 beta

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-a (TNF-alpha), interleukin (IL)-1 beta, 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-alpha and IL-1 beta 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-alpha and IL-1 beta 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-alpha, IL-1 beta and NO seem to play a role in the pathophysiology of this model.

• 出版日期2015-6