Moura José Fernando Bastos, Mota José Maurício Segundo Correia, Leite Caio Abner Vitorino, Wong Deysi Viviana T, Bezerra Nilfácio Prado, Brito Gerly Anne De Castro, Lima Vilma, Cunha Fernando Queiroz, Ribeiro Ronaldo Albuquerque
Department of Physiology and Pharmacology, Medical School, Federal University of Ceará , Brazil.
Int J Radiat Biol. 2015 Jun;91(6):500-9. doi: 10.3109/09553002.2015.1021964. Epub 2015 Mar 20.
To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development.
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.
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.
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.
设计一种新型模型以研究钴 - 60（Co - 60）诱导的放射性口腔黏膜炎，并描述其发生发展过程中涉及的途径。
用Co - 60辐射（10、20、30或35 Gy）处理仓鼠的脸颊。三天后，用针进行口腔黏膜划痕。在照射后第13天（D + 13）对动物实施安乐死。通过我们开发的新评分系统评估大体和微观变化。此外，还评估了口腔黏膜中的中性粒细胞浸润、肿瘤坏死因子 - α（TNF - α）、白细胞介素（IL）-1β、IL - 10、诱导型一氧化氮合酶（iNOS）、一氧化氮（NO）和亚硝酸盐。我们还分别尝试使用己酮可可碱（PTX）和氨基胍（AMG）的药理学方法来确定TNF - α、IL - 1β和iNOS在我们模型中的作用。
我们发现单次给予35 Gy的Co - 60，随后在三天后进行机械划痕，可诱导仓鼠发生口腔黏膜炎。患有黏膜炎的动物体重减轻，生存中位数为13天，这是炎症高峰出现的时间。我们注意到NO、iNOS、TNF - α和IL - 1β水平升高，而IL - 10浓度降低。PTX通过降低炎症介质水平和iNOS表达部分预防了黏膜炎表型。此外，AMG作为iNOS的选择性抑制剂，通过减少NO生成降低了Co - 60诱导的口腔黏膜炎。
我们描述了一种新型的仓鼠兆伏级辐射诱导口腔黏膜炎模型。TNF - α、IL - 1β和NO似乎在该模型的病理生理学中起作用。
