Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI.
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 dys...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Springer Science and Business Media LLC
2020
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| _version_ | 1826265016195612672 |
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| author | Timm, KN Perera, C Ball, V Henry, JA Miller, JJ Kerr, M West, JA Sharma, E Broxholme, J Logan, A Savic, D Dodd, MS Griffin, JL Murphy, MP Heather, LC Tyler, DJ |
| author_facet | Timm, KN Perera, C Ball, V Henry, JA Miller, JJ Kerr, M West, JA Sharma, E Broxholme, J Logan, A Savic, D Dodd, MS Griffin, JL Murphy, MP Heather, LC Tyler, DJ |
| author_sort | Timm, KN |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:17:02Z |
| format | Journal article |
| id | oxford-uuid:2c76214f-fd3c-4d77-bf17-6ba3fcee7a3d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:17:02Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | oxford-uuid:2c76214f-fd3c-4d77-bf17-6ba3fcee7a3d2022-03-26T12:37:28ZEarly detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2c76214f-fd3c-4d77-bf17-6ba3fcee7a3dEnglishSymplectic ElementsSpringer Science and Business Media LLC2020Timm, KNPerera, CBall, VHenry, JAMiller, JJKerr, MWest, JASharma, EBroxholme, JLogan, ASavic, DDodd, MSGriffin, JLMurphy, MPHeather, LCTyler, DJDoxorubicin (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. |
| spellingShingle | Timm, KN Perera, C Ball, V Henry, JA Miller, JJ Kerr, M West, JA Sharma, E Broxholme, J Logan, A Savic, D Dodd, MS Griffin, JL Murphy, MP Heather, LC Tyler, DJ Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title | Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title_full | Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title_fullStr | Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title_full_unstemmed | Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title_short | Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. |
| title_sort | early detection of doxorubicin induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized mri |
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