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Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity

Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting...

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Autores principales: Kabel, Ahmed M., Salama, Samir A., Adwas, Almokhtar A., Estfanous, Remon S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621693/
https://www.ncbi.nlm.nih.gov/pubmed/34832970
http://dx.doi.org/10.3390/ph14111188
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author Kabel, Ahmed M.
Salama, Samir A.
Adwas, Almokhtar A.
Estfanous, Remon S.
author_facet Kabel, Ahmed M.
Salama, Samir A.
Adwas, Almokhtar A.
Estfanous, Remon S.
author_sort Kabel, Ahmed M.
collection PubMed
description Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin-induced cardiac dysfunction in rats. In a model of doxorubicin-induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes. As a result, fraxetin may be put into consideration as a new adjuvant line of therapy on the way to mitigate doxorubicin-induced cardiotoxicity.
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spelling pubmed-86216932021-11-27 Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity Kabel, Ahmed M. Salama, Samir A. Adwas, Almokhtar A. Estfanous, Remon S. Pharmaceuticals (Basel) Article Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity. This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin-induced cardiac dysfunction in rats. In a model of doxorubicin-induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose-dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in a dose-dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes. As a result, fraxetin may be put into consideration as a new adjuvant line of therapy on the way to mitigate doxorubicin-induced cardiotoxicity. MDPI 2021-11-20 /pmc/articles/PMC8621693/ /pubmed/34832970 http://dx.doi.org/10.3390/ph14111188 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kabel, Ahmed M.
Salama, Samir A.
Adwas, Almokhtar A.
Estfanous, Remon S.
Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title_full Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title_fullStr Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title_full_unstemmed Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title_short Targeting Oxidative Stress, NLRP3 Inflammasome, and Autophagy by Fraxetin to Combat Doxorubicin-Induced Cardiotoxicity
title_sort targeting oxidative stress, nlrp3 inflammasome, and autophagy by fraxetin to combat doxorubicin-induced cardiotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621693/
https://www.ncbi.nlm.nih.gov/pubmed/34832970
http://dx.doi.org/10.3390/ph14111188
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