title: A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide.
abstract: OBJECTIVE
  To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Pharmacology, Medical School, Federal University of Ceará , Brazil.
authors.forename: José Fernando Bastos
authors.initials: JF
authors.lastname: Moura
authors.forename: José Maurício Segundo Correia
authors.initials: JM
authors.lastname: Mota
authors.forename: Caio Abner Vitorino
authors.initials: CA
authors.lastname: Leite
authors.forename: Deysi Viviana T
authors.initials: DV
authors.lastname: Wong
authors.forename: Nilfácio Prado
authors.initials: NP
authors.lastname: Bezerra
authors.forename: Gerly Anne De Castro
authors.initials: GA
authors.lastname: Brito
authors.forename: Vilma
authors.initials: V
authors.lastname: Lima
authors.forename: Fernando Queiroz
authors.initials: FQ
authors.lastname: Cunha
authors.forename: Ronaldo Albuquerque
authors.initials: RA
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D003037:Cobalt Radioisotopes / Q000009:adverse effects; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D011882:Radiotherapy, High-Energy / Q000009:adverse effects; D013280:Stomatitis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D003037:Cobalt Radioisotopes; D016207:Cytokines; D006146:Guanidines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D010431:Pentoxifylline
keywords: Megavoltage radiation; animal model; interleukin-1β; nitric oxide; oral mucositis; tumor necrosis factor-α