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Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats

Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been rep...

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Autores principales: Ashour, Abdelkader E., Sayed-Ahmed, Mohamed M., Abd-Allah, Adel R., Korashy, Hesham M., Maayah, Zaid H., Alkhalidi, Hisham, Mubarak, Mohammed, Alhaider, Abdulqader
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359722/
https://www.ncbi.nlm.nih.gov/pubmed/22666520
http://dx.doi.org/10.1155/2012/434195
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author Ashour, Abdelkader E.
Sayed-Ahmed, Mohamed M.
Abd-Allah, Adel R.
Korashy, Hesham M.
Maayah, Zaid H.
Alkhalidi, Hisham
Mubarak, Mohammed
Alhaider, Abdulqader
author_facet Ashour, Abdelkader E.
Sayed-Ahmed, Mohamed M.
Abd-Allah, Adel R.
Korashy, Hesham M.
Maayah, Zaid H.
Alkhalidi, Hisham
Mubarak, Mohammed
Alhaider, Abdulqader
author_sort Ashour, Abdelkader E.
collection PubMed
description Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.
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spelling pubmed-33597222012-06-04 Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats Ashour, Abdelkader E. Sayed-Ahmed, Mohamed M. Abd-Allah, Adel R. Korashy, Hesham M. Maayah, Zaid H. Alkhalidi, Hisham Mubarak, Mohammed Alhaider, Abdulqader Oxid Med Cell Longev Research Article Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH. Hindawi Publishing Corporation 2012 2012-05-10 /pmc/articles/PMC3359722/ /pubmed/22666520 http://dx.doi.org/10.1155/2012/434195 Text en Copyright © 2012 Abdelkader E. Ashour et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ashour, Abdelkader E.
Sayed-Ahmed, Mohamed M.
Abd-Allah, Adel R.
Korashy, Hesham M.
Maayah, Zaid H.
Alkhalidi, Hisham
Mubarak, Mohammed
Alhaider, Abdulqader
Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title_full Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title_fullStr Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title_full_unstemmed Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title_short Metformin Rescues the Myocardium from Doxorubicin-Induced Energy Starvation and Mitochondrial Damage in Rats
title_sort metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359722/
https://www.ncbi.nlm.nih.gov/pubmed/22666520
http://dx.doi.org/10.1155/2012/434195
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