Research Papers:

Low dose radiation prevents doxorubicin-induced cardiotoxicity

Xin Jiang, Yaqiong Hong, Di Zhao, Xinxin Meng, Lijing Zhao, Yanwei Du, Zan Wang, Yan Zheng, Lu Cai and Hongyu Jiang _

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Oncotarget. 2018; 9:332-345. https://doi.org/10.18632/oncotarget.23013

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Xin Jiang1,*, Yaqiong Hong1,*, Di Zhao1, Xinxin Meng1, Lijing Zhao2, Yanwei Du3, Zan Wang4, Yan Zheng5, Lu Cai6 and Hongyu Jiang1

1Department of Health Examination Center, The First Hospital of Jilin University, Changchun, Jilin 130021, China

2The School of Basic Medicine, Jilin University, Changchun, Jilin 130021, China

3Changchun University of Chinese Medicine, Changchun, Jilin 130021, China

4Department of Internal Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, China

5Department of Gerontology, The First Hospital of Jilin University, Changchun, Jilin 130021, China

6Pediatric Research Institute, The Departments of Pediatrics, Radiation Oncology, Pharmacology and Toxicology, The University of Louisville, Louisville, KY 40202, USA

*These authors contributed equally to this work

Correspondence to:

Hongyu Jiang, email: [email protected]

Keywords: low dose radiation; hormesis; adaptive response; doxorubicin; oxidative stress

Received: June 24, 2017     Accepted: November 26, 2017     Published: December 07, 2017


This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

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