Cargando…

Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice

Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess...

Descripción completa

Detalles Bibliográficos
Autores principales: Reis-Mendes, Ana, Dores-Sousa, José Luís, Padrão, Ana Isabel, Duarte-Araújo, Margarida, Duarte, José Alberto, Seabra, Vítor, Gonçalves-Monteiro, Salomé, Remião, Fernando, Carvalho, Félix, Sousa, Emília, Bastos, Maria Lourdes, Costa, Vera Marisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229902/
https://www.ncbi.nlm.nih.gov/pubmed/34073506
http://dx.doi.org/10.3390/ph14060510
_version_ 1783713080439472128
author Reis-Mendes, Ana
Dores-Sousa, José Luís
Padrão, Ana Isabel
Duarte-Araújo, Margarida
Duarte, José Alberto
Seabra, Vítor
Gonçalves-Monteiro, Salomé
Remião, Fernando
Carvalho, Félix
Sousa, Emília
Bastos, Maria Lourdes
Costa, Vera Marisa
author_facet Reis-Mendes, Ana
Dores-Sousa, José Luís
Padrão, Ana Isabel
Duarte-Araújo, Margarida
Duarte, José Alberto
Seabra, Vítor
Gonçalves-Monteiro, Salomé
Remião, Fernando
Carvalho, Félix
Sousa, Emília
Bastos, Maria Lourdes
Costa, Vera Marisa
author_sort Reis-Mendes, Ana
collection PubMed
description Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess if inflammation or oxidative stress-related pathways participate in the cardiotoxicity of MTX, using the mouse as an animal model, at two different age periods (infant or adult mice) using two therapeutic relevant cumulative doses. Histopathology findings showed that MTX caused higher cardiac toxicity in adults. In MTX-treated adults, at the highest dose, noradrenaline cardiac levels decreased, whereas at the lowest cumulative dose, protein carbonylation increased and the expression of nuclear factor kappa B (NF-κB) p65 subunit and of M1 macrophage marker increased. Moreover, MTX-treated adult mice had enhanced expression of NF-κB p52 and tumour necrosis factor (TNF-α), while decreasing interleukin-6 (IL-6). Moreover, while catalase expression significantly increased in both adult and infant mice treated with the lowest MTX cumulative dose, the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione peroxidase only significantly increased in infant animals. Nevertheless, the ratio of GAPDH to ATP synthase subunit beta decreased in adult animals. In conclusion, clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity.
format Online
Article
Text
id pubmed-8229902
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-82299022021-06-26 Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice Reis-Mendes, Ana Dores-Sousa, José Luís Padrão, Ana Isabel Duarte-Araújo, Margarida Duarte, José Alberto Seabra, Vítor Gonçalves-Monteiro, Salomé Remião, Fernando Carvalho, Félix Sousa, Emília Bastos, Maria Lourdes Costa, Vera Marisa Pharmaceuticals (Basel) Article Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess if inflammation or oxidative stress-related pathways participate in the cardiotoxicity of MTX, using the mouse as an animal model, at two different age periods (infant or adult mice) using two therapeutic relevant cumulative doses. Histopathology findings showed that MTX caused higher cardiac toxicity in adults. In MTX-treated adults, at the highest dose, noradrenaline cardiac levels decreased, whereas at the lowest cumulative dose, protein carbonylation increased and the expression of nuclear factor kappa B (NF-κB) p65 subunit and of M1 macrophage marker increased. Moreover, MTX-treated adult mice had enhanced expression of NF-κB p52 and tumour necrosis factor (TNF-α), while decreasing interleukin-6 (IL-6). Moreover, while catalase expression significantly increased in both adult and infant mice treated with the lowest MTX cumulative dose, the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione peroxidase only significantly increased in infant animals. Nevertheless, the ratio of GAPDH to ATP synthase subunit beta decreased in adult animals. In conclusion, clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity. MDPI 2021-05-26 /pmc/articles/PMC8229902/ /pubmed/34073506 http://dx.doi.org/10.3390/ph14060510 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
Reis-Mendes, Ana
Dores-Sousa, José Luís
Padrão, Ana Isabel
Duarte-Araújo, Margarida
Duarte, José Alberto
Seabra, Vítor
Gonçalves-Monteiro, Salomé
Remião, Fernando
Carvalho, Félix
Sousa, Emília
Bastos, Maria Lourdes
Costa, Vera Marisa
Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title_full Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title_fullStr Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title_full_unstemmed Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title_short Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice
title_sort inflammation as a possible trigger for mitoxantrone-induced cardiotoxicity: an in vivo study in adult and infant mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229902/
https://www.ncbi.nlm.nih.gov/pubmed/34073506
http://dx.doi.org/10.3390/ph14060510
work_keys_str_mv AT reismendesana inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT doressousajoseluis inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT padraoanaisabel inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT duartearaujomargarida inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT duartejosealberto inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT seabravitor inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT goncalvesmonteirosalome inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT remiaofernando inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT carvalhofelix inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT sousaemilia inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT bastosmarialourdes inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice
AT costaveramarisa inflammationasapossibletriggerformitoxantroneinducedcardiotoxicityaninvivostudyinadultandinfantmice