Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways

The use of doxorubicin (DOX) as an anthraquinone antineoplastic agent is limited due to its cardiotoxicity. Our previous study suggested that low-dose radiation (LDR) could mitigate the cardiotoxicity induced by DOX via suppressing oxidative stress and cell apoptosis. However, the molecular targets...

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Main Authors: Di Zhao, Xin Jiang, Xinxin Meng, Dandan Liu, Yanwei Du, Lijing Zhao, Hongyu Jiang
Format: Article
Language:English
Published: SAGE Publishing 2023-02-01
Series:Dose-Response
Online Access:https://doi.org/10.1177/15593258231155789
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author Di Zhao
Xin Jiang
Xinxin Meng
Dandan Liu
Yanwei Du
Lijing Zhao
Hongyu Jiang
author_facet Di Zhao
Xin Jiang
Xinxin Meng
Dandan Liu
Yanwei Du
Lijing Zhao
Hongyu Jiang
author_sort Di Zhao
collection DOAJ
description The use of doxorubicin (DOX) as an anthraquinone antineoplastic agent is limited due to its cardiotoxicity. Our previous study suggested that low-dose radiation (LDR) could mitigate the cardiotoxicity induced by DOX via suppressing oxidative stress and cell apoptosis. However, the molecular targets and protective mechanism of LDR are not understood. In the present study, we sought to investigate the mechanisms underlying LDR’s cardioprotection. Balb/c mice were randomly divided into four groups: Control group (no treatment), DOX group, LDR group (75 mGy), and LDR-72 h-DOX group (LDR pretreatment followed by intraperitoneal injection of DOX). Electron microscopy, PCR, and Western blot analyses indicated that LDR pretreatment mitigated changes in mitochondrial morphology caused by DOX, upregulated activity of mitochondrial complexes, and restored ATP levels in cardiomyocytes that were decreased by DOX. Whole genome microarray and PCR analyses showed that mitochondrial-related genes were altered by LDR pretreatment. Thus, our study showed that LDR can protect cardiomyocytes against DOX through improving mitochondrial function and increasing ATP production. This research could inform DOX chemotherapy strategies and provide new insight into the molecule mechanisms underlying the cardioprotective effects of LDR.
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spelling doaj.art-f1652360015c4b07bf976a0d20e4565e2023-02-11T10:03:40ZengSAGE PublishingDose-Response1559-32582023-02-012110.1177/15593258231155789Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial PathwaysDi ZhaoXin JiangXinxin MengDandan LiuYanwei DuLijing ZhaoHongyu JiangThe use of doxorubicin (DOX) as an anthraquinone antineoplastic agent is limited due to its cardiotoxicity. Our previous study suggested that low-dose radiation (LDR) could mitigate the cardiotoxicity induced by DOX via suppressing oxidative stress and cell apoptosis. However, the molecular targets and protective mechanism of LDR are not understood. In the present study, we sought to investigate the mechanisms underlying LDR’s cardioprotection. Balb/c mice were randomly divided into four groups: Control group (no treatment), DOX group, LDR group (75 mGy), and LDR-72 h-DOX group (LDR pretreatment followed by intraperitoneal injection of DOX). Electron microscopy, PCR, and Western blot analyses indicated that LDR pretreatment mitigated changes in mitochondrial morphology caused by DOX, upregulated activity of mitochondrial complexes, and restored ATP levels in cardiomyocytes that were decreased by DOX. Whole genome microarray and PCR analyses showed that mitochondrial-related genes were altered by LDR pretreatment. Thus, our study showed that LDR can protect cardiomyocytes against DOX through improving mitochondrial function and increasing ATP production. This research could inform DOX chemotherapy strategies and provide new insight into the molecule mechanisms underlying the cardioprotective effects of LDR.https://doi.org/10.1177/15593258231155789
spellingShingle Di Zhao
Xin Jiang
Xinxin Meng
Dandan Liu
Yanwei Du
Lijing Zhao
Hongyu Jiang
Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
Dose-Response
title Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
title_full Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
title_fullStr Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
title_full_unstemmed Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
title_short Low-Dose Radiation Reduces Doxorubicin-Induced Myocardial Injury Through Mitochondrial Pathways
title_sort low dose radiation reduces doxorubicin induced myocardial injury through mitochondrial pathways
url https://doi.org/10.1177/15593258231155789
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