In patients who receive radiotherapy for head and neck cancer, oral mucositis is a frequent and serious side effect. The purpose of this study was to develop a noninvasive and quantitative model of oral mucositis in rats, in order to 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 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 to 4 hours after irradiation and returned to a normal level at 24 h. This expression was again observed from Days 3 to 5 and increased significantly on Day 7, which approximately coincided with the histological severity of tissue damage. Subcutaneous administration of palifermin at 3 mg/kg/day for three 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 can 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.
- The American Society for Pharmacology and Experimental Therapeutics