Abstract

Intestinal injury caused by ionizing radiation (IR) is a main clinical issue for patients with cancer receiving abdominal or pelvic radiotherapy. Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that the pineal gland in the brain normally secretes. The study aimed to disclose the potential function of melatonin in intestinal injury induced by IR and its mechanism. Pretreatment with melatonin enhanced the 30-day survival rate of the irradiated mice and promoted the recovery of the intestinal epithelium and hematopoietic function following abdominal irradiation (ABI). Melatonin altered the gene profile of the small intestines from mice following ABI. The enriched biological process terms for melatonin treatment prior to radiation were mainly involved in the immune process. LPS/IL-1-mediated inhibition of RXR Function, TWEAK signaling, and Toll-like receptor signaling were the most activated canonical pathways targeted by melatonin. An upstream analysis network showed that Tripartite motif-containing 24 (TRIM24) was the most significantly inhibited and S100 calcium binding protein A9 (S100A9) activated. TRIM24 activated atherogenesis and cell viability in breast cancer cell lines and S100A9 inhibited the metabolism of amino acids. Melatonin has radioprotective effects on ABI-caused intestinal injury. The mechanisms behind the beneficial effects of melatonin were involved in activation of the immunity. It is necessary to conduct further experiments to explore the underlying mechanisms.

Highlights

  • To detect the effect of melatonin on fatalness for mice caused by Total Body Irradiation (TBI), the 30-day survival rate of mice irradiated with a fatal dose (7.2 Gy) of TBI was first performed (Figure 1A)

  • We found that melatonin promoted the survival rate of mice irradiated with a fatal dose of TBI, suggesting the radioprotective effect of melatonin on the body

  • The hematopoietic system is extremely sensitive to radiation during radiotherapy, which may result in impaired hematopoietic function [12]

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Radiotherapy is a conventional and effective treatment for neoplasm in a clinical context. More than 50 percent of tumor patients receive radiotherapy for curative or palliative purposes [1]. During the radiotherapy of patients with abdominal or pelvic tumors, the small and large bowel is one of the crucial organs at risk during radiotherapy delivered to the abdomen and/or pelvis. A course of clinical radiotherapy usually lasts

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