Radioprotective effect of melatonin on the cervical spinal cord in irradiated rats

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. 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 and E]. The differences among the groups were analyzed using the analysis of variance [ANOVA] test followed by Tukey's multiple comparisons test. 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 20th and 22[nd] weeks after irradiation compared to the radiation-only group. The results support the hypothesis that modulation of VEGF expression by melatonin administration may increase the survival rate of irradiated animals

Evaluation of melatonin for prevention of radiation myelopathy in irradiated cervical spinal cord

Radiation myelopathy [RM] is known as a serious complication of head and neck radiation therapy. Furthermore, the radioprotective roles of melatonin have been investigated on different tissues. The aim of this study was to assess the radio protective effects of melatonin on biochemical, histopathological and clinical manifestations of RM in the rat cervical spinal cord. Four groups of rats were investigated as follows: The control group was treated with vehicle. The second group [melatonin only] was intraperitoneally injected with 100 mg/kg melatonin. The third group's [radiation] cervical spinal cord area was irradiated with 22 Gy cobalt-60 gamma-rays. The fourth group [melatonin plus irradiation] received 100 mg/kg melatonin intraperitoneally, and after 30 minutes their spinal cord area was irradiated with 22 Gy gamma radiation. Five animals from each group were randomly selected. 72 hours, 8 and 22 weeks after irradiation for analysis of malondialdehyde [MDA] and glutathione [GSH] levels, and underwent histopathological studies. The MDA levels in the irradiation group were significantly higher than in the control group [p < 0.001]. Furthermore, the GSH levels in this group were significantly lower than that of those in the control group [p < 0.001]. Administration of melatonin markedly reduced MDA [p < 0.001] and increased GSH [p < 0.05] levels in this group. Demyelination and clinical signs of myelopathy were decreased in the melatonin plus irradiation group in comparison to the irradiated group. Our study confirms the radioprotective effects of melatonin at early stages of biochemical, as well as late histological and clinical changes in the spinal cord