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

Published on Friday, 12 February 2016

Abstract

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.

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- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

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