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A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide.
Int J Radiat Biol 2015; 91(6):500-9IJ

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.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Medical School, Federal University of Ceará , Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25758466

Citation

Moura, José Fernando Bastos, et al. "A Novel Model of Megavoltage Radiation-induced Oral Mucositis in Hamsters: Role of Inflammatory Cytokines and Nitric Oxide." International Journal of Radiation Biology, vol. 91, no. 6, 2015, pp. 500-9.
Moura JF, Mota JM, Leite CA, et al. A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide. Int J Radiat Biol. 2015;91(6):500-9.
Moura, J. F., Mota, J. M., Leite, C. A., Wong, D. V., Bezerra, N. P., Brito, G. A., ... Ribeiro, R. A. (2015). A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide. International Journal of Radiation Biology, 91(6), pp. 500-9. doi:10.3109/09553002.2015.1021964.
Moura JF, et al. A Novel Model of Megavoltage Radiation-induced Oral Mucositis in Hamsters: Role of Inflammatory Cytokines and Nitric Oxide. Int J Radiat Biol. 2015;91(6):500-9. PubMed PMID: 25758466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role of inflammatory cytokines and nitric oxide. AU - Moura,José Fernando Bastos, AU - Mota,José Maurício Segundo Correia, AU - Leite,Caio Abner Vitorino, AU - Wong,Deysi Viviana T, AU - Bezerra,Nilfácio Prado, AU - Brito,Gerly Anne De Castro, AU - Lima,Vilma, AU - Cunha,Fernando Queiroz, AU - Ribeiro,Ronaldo Albuquerque, Y1 - 2015/03/20/ PY - 2015/3/12/entrez PY - 2015/3/12/pubmed PY - 2015/8/5/medline KW - Megavoltage radiation KW - animal model KW - interleukin-1β KW - nitric oxide KW - oral mucositis KW - tumor necrosis factor-α SP - 500 EP - 9 JF - International journal of radiation biology JO - Int. J. Radiat. Biol. VL - 91 IS - 6 N2 - 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. SN - 1362-3095 UR - https://www.unboundmedicine.com/medline/citation/25758466/A_novel_model_of_megavoltage_radiation_induced_oral_mucositis_in_hamsters:_Role_of_inflammatory_cytokines_and_nitric_oxide_ L2 - http://www.tandfonline.com/doi/full/10.3109/09553002.2015.1021964 DB - PRIME DP - Unbound Medicine ER -