Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.ejphar.2021.173955 http://hdl.handle.net/11449/210152 |
Resumo: | The use of doxorubicin (DOX) as an antineoplastic drug is compromised by its cardiotoxicity risk. Although several mechanisms have been proposed for DOX-induced cardiac dysfunction, there is still increased interest in assessing its effects. Likewise, it is important to find protocols that can prevent or minimize the side effects of DOX without hindering its antitumor activity. Thus, this study was designed to investigate the molecular mechanisms underlying DOX cardiotoxicity, with a special focus on cardiac energy metabolism and the ability of Alda-1 (ALDH2 agonist) to prevent DOX-induced cardiac alterations. We explored the effects of DOX on the histological morphology of the myocardium, on lipid profile, and on the expression of genes related to fatty acid metabolism, in the presence and absence of Alda-1 (8 mg/kg body weight; b.wt.). Two DOX treatment protocols were used: a single dose of DOX (4 mg/kg b.wt.); four doses of DOX (4 mg/kg b.wt.), one dose/week, for 4 weeks. Treatment with DOX caused a progressive injury in the cardiac tissue and an increase in the blood total cholesterol, high-density lipoproteins, very low-density lipoproteins and triglyceride, as well as an up-regulation of FABP4 (DOX and DOX + Alda-1 groups) and Slc27a2 (in DOX-treated animals). Alda-1 administration promoted reduction in the severity of the histopathological injuries (after single dose of DOX) and Slc27a2 overexpression was restored. In conclusion, the study revealed novel insights regarding the development of DOX-mediated cardiomyopathy, indicating a relationship between DOX exposure and FABP4 and Slc27a2 overexpression, and confirmed the cardioprotective effect of Alda-1. |
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Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1CardiotoxicityCardioprotectionALDH2 activatorFatty acid binding proteinThe use of doxorubicin (DOX) as an antineoplastic drug is compromised by its cardiotoxicity risk. Although several mechanisms have been proposed for DOX-induced cardiac dysfunction, there is still increased interest in assessing its effects. Likewise, it is important to find protocols that can prevent or minimize the side effects of DOX without hindering its antitumor activity. Thus, this study was designed to investigate the molecular mechanisms underlying DOX cardiotoxicity, with a special focus on cardiac energy metabolism and the ability of Alda-1 (ALDH2 agonist) to prevent DOX-induced cardiac alterations. We explored the effects of DOX on the histological morphology of the myocardium, on lipid profile, and on the expression of genes related to fatty acid metabolism, in the presence and absence of Alda-1 (8 mg/kg body weight; b.wt.). Two DOX treatment protocols were used: a single dose of DOX (4 mg/kg b.wt.); four doses of DOX (4 mg/kg b.wt.), one dose/week, for 4 weeks. Treatment with DOX caused a progressive injury in the cardiac tissue and an increase in the blood total cholesterol, high-density lipoproteins, very low-density lipoproteins and triglyceride, as well as an up-regulation of FABP4 (DOX and DOX + Alda-1 groups) and Slc27a2 (in DOX-treated animals). Alda-1 administration promoted reduction in the severity of the histopathological injuries (after single dose of DOX) and Slc27a2 overexpression was restored. In conclusion, the study revealed novel insights regarding the development of DOX-mediated cardiomyopathy, indicating a relationship between DOX exposure and FABP4 and Slc27a2 overexpression, and confirmed the cardioprotective effect of Alda-1.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Council for Scientific and Technological DevelopmentSao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, BrazilSao Paulo State Univ, Med Sch, Botucatu, SP, BrazilSao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, BrazilSao Paulo State Univ, Med Sch, Botucatu, SP, BrazilFAPESP: FAPESP 2012/17280FAPESP: 2014/09740-0National Council for Scientific and Technological Development: CNPq 303435/2016Elsevier B.V.Universidade Estadual Paulista (Unesp)Menezes Souza, Leonardo da Cunha [UNESP]Fernandes, Fabio Henrique [UNESP]Presti, Paula Torres [UNESP]Anjos Ferreira, Ana Lucia [UNESP]Favero Salvadori, Daisy Maria [UNESP]2021-06-25T12:41:14Z2021-06-25T12:41:14Z2021-05-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article7http://dx.doi.org/10.1016/j.ejphar.2021.173955European Journal Of Pharmacology. Amsterdam: Elsevier, v. 898, 7 p., 2021.0014-2999http://hdl.handle.net/11449/21015210.1016/j.ejphar.2021.173955WOS:000632516600003Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengEuropean Journal Of Pharmacologyinfo:eu-repo/semantics/openAccess2024-09-03T13:17:52Zoai:repositorio.unesp.br:11449/210152Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:17:52Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
title |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
spellingShingle |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 Menezes Souza, Leonardo da Cunha [UNESP] Cardiotoxicity Cardioprotection ALDH2 activator Fatty acid binding protein |
title_short |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
title_full |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
title_fullStr |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
title_full_unstemmed |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
title_sort |
Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1 |
author |
Menezes Souza, Leonardo da Cunha [UNESP] |
author_facet |
Menezes Souza, Leonardo da Cunha [UNESP] Fernandes, Fabio Henrique [UNESP] Presti, Paula Torres [UNESP] Anjos Ferreira, Ana Lucia [UNESP] Favero Salvadori, Daisy Maria [UNESP] |
author_role |
author |
author2 |
Fernandes, Fabio Henrique [UNESP] Presti, Paula Torres [UNESP] Anjos Ferreira, Ana Lucia [UNESP] Favero Salvadori, Daisy Maria [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Menezes Souza, Leonardo da Cunha [UNESP] Fernandes, Fabio Henrique [UNESP] Presti, Paula Torres [UNESP] Anjos Ferreira, Ana Lucia [UNESP] Favero Salvadori, Daisy Maria [UNESP] |
dc.subject.por.fl_str_mv |
Cardiotoxicity Cardioprotection ALDH2 activator Fatty acid binding protein |
topic |
Cardiotoxicity Cardioprotection ALDH2 activator Fatty acid binding protein |
description |
The use of doxorubicin (DOX) as an antineoplastic drug is compromised by its cardiotoxicity risk. Although several mechanisms have been proposed for DOX-induced cardiac dysfunction, there is still increased interest in assessing its effects. Likewise, it is important to find protocols that can prevent or minimize the side effects of DOX without hindering its antitumor activity. Thus, this study was designed to investigate the molecular mechanisms underlying DOX cardiotoxicity, with a special focus on cardiac energy metabolism and the ability of Alda-1 (ALDH2 agonist) to prevent DOX-induced cardiac alterations. We explored the effects of DOX on the histological morphology of the myocardium, on lipid profile, and on the expression of genes related to fatty acid metabolism, in the presence and absence of Alda-1 (8 mg/kg body weight; b.wt.). Two DOX treatment protocols were used: a single dose of DOX (4 mg/kg b.wt.); four doses of DOX (4 mg/kg b.wt.), one dose/week, for 4 weeks. Treatment with DOX caused a progressive injury in the cardiac tissue and an increase in the blood total cholesterol, high-density lipoproteins, very low-density lipoproteins and triglyceride, as well as an up-regulation of FABP4 (DOX and DOX + Alda-1 groups) and Slc27a2 (in DOX-treated animals). Alda-1 administration promoted reduction in the severity of the histopathological injuries (after single dose of DOX) and Slc27a2 overexpression was restored. In conclusion, the study revealed novel insights regarding the development of DOX-mediated cardiomyopathy, indicating a relationship between DOX exposure and FABP4 and Slc27a2 overexpression, and confirmed the cardioprotective effect of Alda-1. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T12:41:14Z 2021-06-25T12:41:14Z 2021-05-05 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.ejphar.2021.173955 European Journal Of Pharmacology. Amsterdam: Elsevier, v. 898, 7 p., 2021. 0014-2999 http://hdl.handle.net/11449/210152 10.1016/j.ejphar.2021.173955 WOS:000632516600003 |
url |
http://dx.doi.org/10.1016/j.ejphar.2021.173955 http://hdl.handle.net/11449/210152 |
identifier_str_mv |
European Journal Of Pharmacology. Amsterdam: Elsevier, v. 898, 7 p., 2021. 0014-2999 10.1016/j.ejphar.2021.173955 WOS:000632516600003 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
European Journal Of Pharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
7 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1810021398851092480 |