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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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 |
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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 |
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