Establishment of an X-ray irradiation-induced glossitis model in rats: biphasic elevation of proinflammatory cytokines and chemokines.
Oral mucositis is a frequent and serious side effect in patients who receive radiotherapy for head and neck cancer. The purpose of this study was to develop a noninvasive and quantitative model of oral mucositis in rats, investigate the pathophysiology, and evaluate the efficacy of pharmacological interventions. Rats received a single dose of 15 Gy of X-rays to the snout after shielding of the remainder of the rat body with lead plates to protect the body from irradiation (day 0). After irradiation, the macroscopic area of tongue injury gradually increased. The total area of injury and the ulcer-like area reached a maximum on day 7 and then gradually decreased until disappearance on day 28. Expression of proinflammatory cytokines and chemokines occurred transiently within 1-4 hours after irradiation and returned to a normal level at 24 hours. This expression was again observed from days 3 to 5 and increased significantly on day 7, which approximately coincided with the histologic severity of tissue damage. Subcutaneous administration of palifermin at 3 mg/kg per day for 3 consecutive days before irradiation completely prevented ulcer formation in this model. In conclusion, we established a novel model of glossitis in rats, induced by X-ray irradiation, in which biphasic elevations of expression of proinflammatory cytokines and chemokines could be monitored. This model is considered useful to investigate the pathophysiology of oral mucositis and evaluate the preventive effect of pharmacological interventions on oral mucositis induced by X-ray irradiation.
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan (T.N., T.I.); and Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan (T.N., N.U., M.S., K.S.).
Takako
T
Nakashima
Naoya
N
Uematsu
Masafumi
M
Shibamori
Kazushi
K
Sakurai
Tatsuhiro
T
Ishida
D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005928:Glossitis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D052016:Mucositis / Q000188:drug therapy / Q000209:etiology; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014059:Tongue / Q000378:metabolism / Q000473:pathology; D014965:X-Rays
D018925:Chemokines; D016207:Cytokines; D011837:Radiation-Protective Agents; D051523:Fibroblast Growth Factor 7