Research Paper Advance Articles

Dexrazoxane ameliorates radiation-induced heart disease in a rat model

Long Li1, , Xiaoqi Nie1, , Peng Zhang1, , Yongbiao Huang1, , Li Ma1, , Fang Li1, , Minxiao Yi1, , Wan Qin1, , Xianglin Yuan1, ,

  • 1 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

Received: July 8, 2020       Accepted: November 3, 2020       Published: January 2, 2021      

https://doi.org/10.18632/aging.202332
How to Cite

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug administered with chemotherapy, on radiation-induced heart disease (RIHD) in a rat model. Male Sprague-Dawley rats were irradiated with a single dose of 20 Gy to the heart and treated with dexrazoxane at the time of irradiation and for 12 subsequent weeks. Dexrazoxane suppressed radiation-induced myocardial apoptosis and significantly reversed changes in serum cardiac troponin I levels and histopathological characteristics six months post-radiation. Treatment with dexrazoxane did not alter the radiosensitivity of thoracic tumors in a tumor formation experiment using male nude Balb/C mice with tumors generated by H292 cells. Dexrazoxane reduced the accumulation of reactive oxygen species in rat cardiac tissues, but not in tumors in nude mice. Transcriptome sequencing showed that IKBKE, MAP3K8, NFKBIA, and TLR5, which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Immunohistochemistry revealed that dexrazoxane significantly decreased NF-κB p65 expression in cardiomyocytes. These findings suggest dexrazoxane may protect against RIHD by suppressing apoptosis and oxidative stress in cardiomyocytes.

Abbreviations

DZR: dexrazoxane; RIHD: radiation induced heart disease; cTnI: cardiac troponin I; MACE: major adverse cardiac events; MHD: mean heart dose; OS: oxidative stress; ROS: reactive oxygen species; CON: control group; TEM: transmission electron microscopy; EF: left ventricular ejection fraction; DHE: dihydroethidium; i.p: intraperitoneal; C-caspase-3: cleaved caspase-3.