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

ABSTRACT

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