Evaluation of the Radioprotective Effects of Melatonin Against Ionizing Radiation-Induced Muscle Tissue Injury

Abstract

Background: Radiotherapy (RT) is a treatment method for cancer using ionizing radiation (IR). The interaction between IR with tissues produces free radicals that cause biological damages.As the largest organ in the human body, the skeletal muscles may be affected by detrimental effects of ionizing radiation. To eliminate these side effects, we used melatonin, a major product secreted by the pineal gland in mammals, as a radioprotective agent. Materials and Methods: For this study, a total of sixty male Wistar rats were used. They were allotted to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). Rats’ right hind legs were irradiated with 30 Gy single dose of gamma radiation, while 100 mg/kg of melatonin was given to them 30 minutes before irradiation and 5 mg/ kg once daily afternoon for 30 days. Five rats in each group were sacrificed 4, 12 and 20 weeks after irradiation for histological and biochemical examinations. Results: Our results showed radiation-induced biochemical, histological and electrophysiological changes in normal rats’ gastrocnemius muscle tissues. Biochemical analysis showed that malondialdehyde (MDA) levels significantly elevated in R group (P<0.001) and reduced significantly in M and MR groups after 4, 12, and 20 weeks (P<0.001), However, the activity of catalase (CAT) and superoxide dismutase(SOD)decreased in the R group and increased in M and MR groups for the same periods of time compared with the C group (P<0.001), while melatonin administration inverted these effects( P<0.001).Histopathological examination showed significant differences between R group for different parameters compared with other groups (P<0.001). However, the administration of melatonin prevented these effects(P<0.001). Electromyography (EMG) examination showed that the compound action potential (CMAP) value in the R group was significantly reduced compared to the effects in the C and M groups after 12 and 20 weeks (P<0.001). The administration of melatonin also reversed these effects (P<0.001). Conclusion: Melatonin can improve biochemical, electrophysiological and morphological features of irradiated gastrocnemius muscle tissues.Our recommendation is that melatonin should be administered in optimal dose. For effective protection of muscle tissues, and increased therapeutic ratio of radiation therapy, this should be done within a long period of time.