Radioprotective Effect of Melatonin on The Cervical Spinal Cord in Irradiated Rats

OBJECTIVE: It has been suggested that the vascular endothelial growth factor (VEGF) gene expression plays an important role in radiation-induced injury to the spinal cord. This study assesses the radioprotective effects of N-acetyl-5-methoxytryptamine (melatonin) through its modulation of VEGF expression after localized irradiation of the cervical spinal cord. MATERIALS AND METHODS: In this experimental study, we divided 192 male rats into four groups: 1. control (n=48); 2. rats that received an intraperitoneal (IP) injection of melatonin (n=48); 3. rats that received an IP injection of melatonin 30 minutes prior to cervical spinal cord gamma irradiation [dose: 22 Gy; (n=48)]; and 4. rats that received an IP injection of vehicle prior to spinal cord irradiation (n=48). The changes in VEGF expression were assessed using real-time RT-PCR and enzyme-linked immunosorbent assays. Samples for light microscopy were stained with hematoxylin and eosin (H&E). The differences among the groups were analyzed using the analysis of variance (ANOVA) test followed by Tukey’s multiple comparisons test. RESULTS: Up-regulation of VEGF expression was observed from 8 to 22 weeks after irradiation (p<0.05). Paralysis and other radiation-induced myelopathy manifestations developed within 22 weeks after irradiation. VEGF expression in the melatonin pre-treatment group significantly down-regulated in the 20(th) and 22(nd) weeks after irradiation compared to the radiation-only group. CONCLUSION: The results support the hypothesis that modulation of VEGF expression by melatonin administration may increase the survival rate of irradiated animals.