Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin.

Bagher Farhood,Akbar Aliasgharzadeh,Mehran Mohseni,Elahe Motevaseli,Farzad Nouruzi,Ahmed Eleojo Musa,Peyman Amini,Ghorbangol Ashabi,Dheyauldeen Shabeeb,Masoud Najafi,Hana Saffar,Saeed Rezapoor,Habiballah Moradi

doi:10.3390/medicina55070317

Abstract

Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

Highlights

Heart tissue is one of the late responding tissues to ionizing radiation
This study has shown that irradiation of the hearts of rats leads to activation of IL-4 and its downstream genes: IL4ra1, Duox1, and Duox2
The expression of Duox1 was increased without upregulation of IL-13, which may indicate a role of other mediators such as IL-4 in the expression of Duox1

Summary

Introduction

Heart tissue is one of the late responding tissues to ionizing radiation. Cardiovascular diseases are among the common non-cancerous disorders for people who have been exposed to ionizingMedicina 2019, 55, 317; doi:10.3390/medicina55070317 www.mdpi.com/journal/medicinaMedicina 2019, 55, 317 radiation [1]. The most obvious examples of radiation-induced heart diseases include increased risk of heart failure, attack, and ischemia among Chernobyl, Hiroshima, and Nagasaki survivors [2,3]. Some radiobiological studies have reported that damages to other organs such as the respiratory system or kidneys may lead to changes in normal physiological functions of the heart and induce heart damage markers [5]. Studies have reported that pathological heart changes may take months to years after exposure to ionizing radiation to appear. Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. We evaluated the upregulation of Duox and Duox pathways in hearts following chest irradiation in rats and detected possible attenuation of them by melatonin.

Objectives

Methods

Discussion

Conclusion