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Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats

Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-infla...

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Autores principales: Sari, Flori R., Arozal, Wawaimuli, Watanabe, Kenichi, Harima, Meilei, Veeravedu, Punniyakoti T., Thandavarayan, Rajarajan A., Suzuki, Kenji, Arumugam, Somasundaram, Soetikno, Vivian, Kodama, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053802/
http://dx.doi.org/10.3390/ph4030551
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author Sari, Flori R.
Arozal, Wawaimuli
Watanabe, Kenichi
Harima, Meilei
Veeravedu, Punniyakoti T.
Thandavarayan, Rajarajan A.
Suzuki, Kenji
Arumugam, Somasundaram
Soetikno, Vivian
Kodama, Makoto
author_facet Sari, Flori R.
Arozal, Wawaimuli
Watanabe, Kenichi
Harima, Meilei
Veeravedu, Punniyakoti T.
Thandavarayan, Rajarajan A.
Suzuki, Kenji
Arumugam, Somasundaram
Soetikno, Vivian
Kodama, Makoto
author_sort Sari, Flori R.
collection PubMed
description Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-inflammatory drug. This study was designed to evaluate whether carvedilol exerts a protective role against inflammation-mediated cardiotoxicity in the daunorubicin (DNR)-induced rats. Carvedilol was administered orally to the rats every day for 6 weeks at a cumulative dose of 9 mg/kg body weight DNR. DNR significantly induced cardiac damage and worsened cardiac function as well as increased cardiac mast cell density, elevating the myocardial protein and mRNA expression levels of tumor necrosis factor-α, vascular cell adhesion molecule-1, inter-cellular adhesion molecule-1, nuclear factor kappa-B, cyclooxygenase-2, monocyte chemotactic protein -1 and interleukin -6 compared to that in the control group. Cotreatment with carvedilol significantly attenuated the myocardial protein and mRNA expression levels of these inflammatory markers, decreased cardiac mast cell density, improved histological cardiac damage and cardiac functions. In conclusion, inflammation plays a significant role in DNR-induced cardiotoxicity, and carvedilol contributes to cardioprotection against inflammation-mediated cardiotoxicity in DNR-induced rats through its anti-inflammatory mechanism.
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spelling pubmed-40538022014-06-12 Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats Sari, Flori R. Arozal, Wawaimuli Watanabe, Kenichi Harima, Meilei Veeravedu, Punniyakoti T. Thandavarayan, Rajarajan A. Suzuki, Kenji Arumugam, Somasundaram Soetikno, Vivian Kodama, Makoto Pharmaceuticals (Basel) Article Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-inflammatory drug. This study was designed to evaluate whether carvedilol exerts a protective role against inflammation-mediated cardiotoxicity in the daunorubicin (DNR)-induced rats. Carvedilol was administered orally to the rats every day for 6 weeks at a cumulative dose of 9 mg/kg body weight DNR. DNR significantly induced cardiac damage and worsened cardiac function as well as increased cardiac mast cell density, elevating the myocardial protein and mRNA expression levels of tumor necrosis factor-α, vascular cell adhesion molecule-1, inter-cellular adhesion molecule-1, nuclear factor kappa-B, cyclooxygenase-2, monocyte chemotactic protein -1 and interleukin -6 compared to that in the control group. Cotreatment with carvedilol significantly attenuated the myocardial protein and mRNA expression levels of these inflammatory markers, decreased cardiac mast cell density, improved histological cardiac damage and cardiac functions. In conclusion, inflammation plays a significant role in DNR-induced cardiotoxicity, and carvedilol contributes to cardioprotection against inflammation-mediated cardiotoxicity in DNR-induced rats through its anti-inflammatory mechanism. MDPI 2011-03-17 /pmc/articles/PMC4053802/ http://dx.doi.org/10.3390/ph4030551 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Sari, Flori R.
Arozal, Wawaimuli
Watanabe, Kenichi
Harima, Meilei
Veeravedu, Punniyakoti T.
Thandavarayan, Rajarajan A.
Suzuki, Kenji
Arumugam, Somasundaram
Soetikno, Vivian
Kodama, Makoto
Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title_full Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title_fullStr Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title_full_unstemmed Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title_short Carvedilol Attenuates Inflammatory-Mediated Cardiotoxicity in Daunorubicin-Induced Rats
title_sort carvedilol attenuates inflammatory-mediated cardiotoxicity in daunorubicin-induced rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053802/
http://dx.doi.org/10.3390/ph4030551
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