Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats

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dc.contributor.authorPolegato, Bertha Furlan [UNESP]
dc.contributor.authorMinicucci, Marcos Ferreira [UNESP]
dc.contributor.authorAzevedo, Paula Schmidt [UNESP]
dc.contributor.authorCarvalho, Robson Francisco [UNESP]
dc.contributor.authorChiuso-Minicucci, Fernanda [UNESP]
dc.contributor.authorPereira, Elenize Jamas [UNESP]
dc.contributor.authorPaiva, Sergio Alberto Rupp [UNESP]
dc.contributor.authorZornoff, Leonardo Antonio Mamede [UNESP]
dc.contributor.authorOkoshi, Marina Politi [UNESP]
dc.contributor.authorMatsubara, Beatriz Bojikian [UNESP]
dc.contributor.authorMatsubara, Luiz Shiguero [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-10-21T13:08:55Z
dc.date.available2015-10-21T13:08:55Z
dc.date.issued2015-01-01
dc.description.abstractBackground: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/- 0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.en
dc.description.affiliationUnespUniversidade Estadual Paulista, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu
dc.description.affiliationUnespUniversidade Estadual Paulista, Departamento de Morfologia, Instituto de Biociências de Botucatu
dc.description.affiliationUnespUniversidade Estadual Paulista, Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu
dc.format.extent1924-1933
dc.identifierhttp://www.karger.com/Article/FullText/374001
dc.identifier.citationCellular Physiology And Biochemistry. Basel: Karger, v. 35, n. 5, p. 1924-1933, 2015.
dc.identifier.doi10.1159/000374001
dc.identifier.fileWOS000353713900022.pdf
dc.identifier.issn1015-8987
dc.identifier.lattes5406518799128485
dc.identifier.lattes6990977122340795
dc.identifier.lattes4463138671998432
dc.identifier.lattes6309835137998766
dc.identifier.lattes5016839015394547
dc.identifier.lattes1213140801402647
dc.identifier.lattes7438704034471673
dc.identifier.orcid0000-0002-4901-7714
dc.identifier.orcid0000-0002-9831-8820
dc.identifier.orcid0000-0002-5843-6232
dc.identifier.urihttp://hdl.handle.net/11449/128314
dc.identifier.wosWOS:000353713900022
dc.language.isoeng
dc.publisherKarger
dc.relation.ispartofCellular Physiology And Biochemistry
dc.relation.ispartofjcr5.500
dc.relation.ispartofsjr1,561
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectIsolated heart studyen
dc.subjectCytokinesen
dc.subjectPhospholambanen
dc.subjectRyanodine receptoren
dc.subjectSerca-2aen
dc.subjectMatrix metalloproteinaseen
dc.subjectDoxorubicinen
dc.subjectAcute cardiotoxicityen
dc.titleAcute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in ratsen
dc.typeArtigo
dcterms.licensehttp://www.karger.com/Services/RightsPermissions
dcterms.rightsHolderKarger
unesp.author.lattes5406518799128485
unesp.author.lattes6990977122340795
unesp.author.lattes4463138671998432
unesp.author.lattes6309835137998766
unesp.author.lattes5016839015394547[8]
unesp.author.lattes1213140801402647[3]
unesp.author.lattes7438704034471673
unesp.author.lattes4563764623232492[1]
unesp.author.orcid0000-0002-4901-7714[4]
unesp.author.orcid0000-0002-9831-8820[8]
unesp.author.orcid0000-0002-5843-6232[3]
unesp.author.orcid0000-0002-2875-9532[1]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Medicina, Botucatupt

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Artigos - Clínica Médica - FMB
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