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NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes

The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Oth...

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Autores principales: Brandolini, Laura, Antonosante, Andrea, Giorgio, Cristina, Bagnasco, Michela, d’Angelo, Michele, Castelli, Vanessa, Benedetti, Elisabetta, Cimini, Annamaria, Allegretti, Marcello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591859/
https://www.ncbi.nlm.nih.gov/pubmed/33110169
http://dx.doi.org/10.1038/s41598-020-75394-x
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author Brandolini, Laura
Antonosante, Andrea
Giorgio, Cristina
Bagnasco, Michela
d’Angelo, Michele
Castelli, Vanessa
Benedetti, Elisabetta
Cimini, Annamaria
Allegretti, Marcello
author_facet Brandolini, Laura
Antonosante, Andrea
Giorgio, Cristina
Bagnasco, Michela
d’Angelo, Michele
Castelli, Vanessa
Benedetti, Elisabetta
Cimini, Annamaria
Allegretti, Marcello
author_sort Brandolini, Laura
collection PubMed
description The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death.
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spelling pubmed-75918592020-10-28 NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes Brandolini, Laura Antonosante, Andrea Giorgio, Cristina Bagnasco, Michela d’Angelo, Michele Castelli, Vanessa Benedetti, Elisabetta Cimini, Annamaria Allegretti, Marcello Sci Rep Article The progressive consumption growth of non-steroidal anti-inflammatory drugs (NSAIDs) has progressively raised the attention toward the gastrointestinal, renal, and cardiovascular toxicity. Increased risk of cardiovascular diseases was strictly associated with the usage of COX-2 selective NSAIDs. Other studies allowed to clarify that the cardiovascular risk is not limited to COX-2 selective but also extended to non-selective NSAIDs, such as Diclofenac and Ketoprofen. To date, although a less favorable cardiovascular risk profile for Diclofenac as compared to Ketoprofen is reported, the mechanisms through which NSAIDs cause adverse cardiovascular events are not entirely understood. The present study aimed to evaluate the effects of Ketoprofen in comparison with Diclofenac in immortalized human cardiomyocytes. The results obtained highlight the dose-dependent cardiotoxicity of Diclofenac compared to Ketoprofen. Despite both drugs induce the increase in ROS production, decrease of mitochondrial membrane potential, and proteasome activity modulation, only Diclofenac exposure shows a marked alteration of these intracellular parameters, leading to cell death. Noteworthy, Diclofenac decreases the proteasome 26S DC and this scenario may be dependent on the intracellular overload of oxidized proteins. The data support the hypothesis that immortalized human cardiomyocytes exposed to Ketoprofen are subjected to tolerable stress events, conversely Diclofenac exposition triggers cell death. Nature Publishing Group UK 2020-10-27 /pmc/articles/PMC7591859/ /pubmed/33110169 http://dx.doi.org/10.1038/s41598-020-75394-x Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Brandolini, Laura
Antonosante, Andrea
Giorgio, Cristina
Bagnasco, Michela
d’Angelo, Michele
Castelli, Vanessa
Benedetti, Elisabetta
Cimini, Annamaria
Allegretti, Marcello
NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title_full NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title_fullStr NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title_full_unstemmed NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title_short NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
title_sort nsaids-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591859/
https://www.ncbi.nlm.nih.gov/pubmed/33110169
http://dx.doi.org/10.1038/s41598-020-75394-x
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