Establishment of an X-ray Irradiation-Induced Glossitis Model in Rats: Biphasic Elevation of Proinflammatory Cytokines and Chemokines

Abstract

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.

Protective effect of FGF-2 and low-molecular-weight heparin/protamine nanoparticles on radiation-induced healing-impaired wound repair in rats

“…Lead shielding for X-irradiation is used to protect sensitive organs in animal study as well as in radiation therapy. When rats received a single dose of 15 Gy of X-rays to the snout after shielding of the remainder of the rat body with 0.5 mm-thickness lead plates in the X-ray irradiation-induced glossitis model [ 24 ]. We previously used 3 mm-thick lead shield to X-irradiation, which showed a shielding effect [ 8 , 10 ].…”

Novel Submicronized Rebamipide Liquid with Moderate Viscosity: Significant Effects on Oral Mucositis in Animal Models

“…Rat Model of Radiation-Induced Glossitis We recently developed an experimental model of glossitis whereby male rats were exposed to a single dose of X-irradiation to induce glossitis, 21) and this model was used to evaluate the oral mucositis preventive effect of rebamipide liquid. Briefly, 7-weekold male rats were anesthetized with intraperitoneal 45 mg/ kg dose of pentobarbital sodium, and two lead plates (each 0.5 mm thick) were used to shield the animal from exposure to irradiation except for the snout (the region of the head anterior to the eyes), which was irradiated with a single 15 Gy dose using an X-irradiation system (CP160, Faxitron X-Ray Corporation, Illinois, U.S.A.).…”

“…21) Liquid I was intra-orally administered into rat six times a day at 0.5 mL/ kg doses daily for 14 d, starting 7 d before irradiation. The injured surface areas were measured on Day 7 after irradiation (Fig.…”

T cell abundance in blood predicts acute organ toxicity in chemoradiotherapy for head and neck cancer

“…More recently, genetic factors [ 11 , 12 ] and several inflammation markers [ 8 ] have been identified as additional putative risk factors. In animal models, for instance, increased tissue expression of COX-2 [ 13 , 14 ], pro-inflammatory cytokines such as TNFα, IL-6 and IL-1β, or chemokines like CXCL1 and CCL2 were associated with radiation-induced mucositis [ 15 ]. In contrast, data on human non-tumor tissue are scarce, with the exception of a report on mucosal and submucosal leukocyte infiltration at the end of the second radiation treatment week, when focal mucositis usually occurs [ 16 ].…”