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 radio-protective effect of melatonin on whole body irradiation induced liver tissue damage

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study, thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin [30 mg/kg on the first day and 30 mg/kg on the following days], group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal [IP] injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde [MDA] and glutathione [GSH]. Each data point represents mean ñ standard error on the mean [SEM] of at least eight animals per group. A one-way analysis of variance [ANOVA] was performed to compare different groups, followed by Tukey's multiple comparison tests [p<0.05]. The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin [30 mg/kg] were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation

Radioprotective effect of melatonin in reducing oxidative stress in rat lenses

Ocular morbidity is widely observed when radiotherapy includes the orbit. Oxidative stress generated by irradiation is responsible for this complication. In different studies, it has been shown that melatonin has antioxidative properties and a radioprotective role. The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury in rats' lenses after total cranial irradiation. Thirty-six adult female Sprague-Dawley rats were divided into six groups. Group I was the control group, group II only received total cranial gamma irradiation of 5 Gy, group III was exposed as the second group but at the dose of 8 Gy, group IV received 30 mg/kg melatonin 30 minutes prior to radiation plus total cranial irradiation of 5 Gy plus 5 mg/kg melatonin daily through intraperitoneal injection for ten days after irradiation, group V was treated similar to the fourth group, i. e. received irradiation plus melatonin, but at the dose of 8 Gy, and group VI only received melatonin [30 mg/kg on the first day and 5 mg/kg on the following days]. Ten days after irradiation, all rats were sacrificed and their eyes were enucleated to measure the biochemical parameters i. e. malondialdehyde [MDA] and glutathione [GSH]. The levels of MDA in rat lenses increased and the levels of glutathione in lenses decreased after gamma ray irradiation but these parameters were still within normal limits in rats that received melatonin. It could be concluded that melatonin is useful in preventing radiation-induced oxidative injury due to its antioxidative and free radical scavenging properties

[ dosimetric evaluation of organs at risk in prostate radiation therapy using a MAGIC gel dosimeter]

Multiple fields and presence of hetrerogeneities create complex dose distributions that need three dimentisonal dosimetry. In this work, we investigated MR-based MAGIC gel dosimetry as a three-dimentional dosimetry technique to measure the delivered dose to bladder and rectum in prostate radiation therapy. A heterogeneous slab phantom including bones was made. Paired cubes in the phantom representing bladder and prostate and a cylindrical container representing rectum were filled with MAGIC gel and placed in the anthropomorphic pelvic phantom. The phantom was irradiated with four beams as planned using a treatment planning system [TPS]. Magnetic resonance transverse relaxation rate images were acquired and turned into dose distribution maps using a calibration curve. This calibration curve was obtained by linear fitting to R2 values of 4 test tubes against their given known doses. Image processing and data analysis were preformed in MATLAB 7 software. The gel dosimeter was validated using an ionization chamber. Dose maps and dose volume histograms [DVHs] were compared with dose distributions and DVHs of the TPS. Mean "distance-to-agreement" and mean "does difference" were 2.98 mm and 6.2%, respectively, in the comparison of profiles obtained from ionization chamber and gel dostimetry. Mean relative difference of DHVs between gel dosimetry and TPs data were 3.04%, 10.4% and 11.7%,for prostate, bladder and rectum, respectively. Gel dosimetry is a good method for three dimensional dosimetry although it has a low precision in high close gradient regions. This method can be used for evaluation of complicated dose distribution accuracy in 3D conformal radiotherapy, especially in presence of heterogeneities

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