Cytoprotective effects of amifostine and melatonin against radiation-induced oral mucositis in rats

Amifostine (AMI) protects against radiotherapy (RT)-induced toxicities and melatonin (MEL) is a potent free radical scavenger. This study was performed to investigate the protective effects of AMI and MEL on radiation-induced oral mucositis (ROM).

Thirty female Sprague-Dawley rats were randomly divided into five groups as follows: the control (Cont), RT alone (RT), RT+AMI, RT+MEL, and RT+AMI+MEL. RT groups were irradiated with a single dose of 15 Gy to the head. AMI (200 mg/kg) and MEL (100 mg/kg) were administered intraperitoneally 1 hour before radiation exposure. Changes in body weights and histology in irradiated tongue tissues were analyzed 10 days after exposure.

AMI and/or MEL treatment significantly prevented irradiation-induced body weight loss and promoted epithelial cell proliferation. Mean epithelial thickness was markedly higher in the AMI+MEL group (73.9 ± 9.7 um) than in the RT group (28.8 ± 13.9 um) (P<0.001), and Ki67 expression was significantly higher in AMI, MEL, and AMI+MEL groups than in the RT group (p < 0.001). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) revealed that AMI+MEL treatment significantly inhibited radiation-induced apoptosis in irradiated epithelium (p=0.006).

AMI and MEL administrations similarly protected animals from ROM and, when co-administered, had additive effects.