Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Kerstin Timm, Charith Perera, Vicky Ball, John Henry, Jack Miller, Matthew Kerr, James West, Eshita Sharma, John Broxholme, Angela Logan, Dragana Savic, Michael Dodd, Julian L. Griffin, Michael Murphy, Lisa C Heather, Damian J Tyler

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity.
Original languageEnglish
Article number692
Number of pages10
JournalCommunications Biology
Volume3
DOIs
Publication statusPublished - 19 Nov 2020
Externally publishedYes

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine (miscellaneous)

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