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dc.contributor.author
Hernández, Matías
dc.contributor.author
Wicz, Susana
dc.contributor.author
Corral, Ricardo Santiago
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dc.date.available
2018-05-31T19:23:41Z
dc.date.issued
2016-11
dc.identifier.citation
Hernández, Matías; Wicz, Susana; Corral, Ricardo Santiago; Cardioprotective actions of curcumin on the pathogenic NFAT/COX-2/prostaglandin E2 pathway induced during Trypanosoma cruzi infection; Elsevier Gmbh; Phytomedicine; 23; 12; 11-2016; 1392-1400
dc.identifier.issn
0944-7113
dc.identifier.uri
http://hdl.handle.net/11336/46880
dc.description.abstract
Background: Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca2+/NFAT cascade in cardiomyocytes, leading to cyclooxygenase type 2 (COX-2) induction and increased release of prostanoids and prohypertrophic peptides. Purpose: To determine whether the well-known cardioprotective and anti-inflammatory effects of curcumin (Cur) could be helpful to interfere with this key machinery for pathogenesis of Chagas myocarditis. Study Design: Cur treatment was evaluated through in vivo studies using a murine model of acute T. cruzi infection and in vitro experiments using ET-1-stimulated and parasite-infected mouse cardiomyocytes. Methods: Cur-treated and untreated infected mice were followed-up to estimate survival postinfection and heart tissues from both groups were analyzed for inflammatory infiltration by histopathology, whereas parasite load, induction of arachidonic acid pathway and natriuretic peptide expression were determined by real-time PCR. Molecular analysis of Cur myocardial targets included intracellular calcium measurement, NFAT and COX-2 induction in transfected cells, and assessment of NFAT, COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) levels by immunoblotting, prostaglandin E2 (PGE2) by ELISA, b-type natriuretic peptide (BNP) by real-time PCR, and PGE2/EP4 receptor/BNP interaction by transwell experiments. Results: Cur treatment of acute Chagas mice enhanced survival and proved to hinder relevant inflammatory processes in the heart, including leukocyte recruitment, activation of the eicosanoid pathway and BNP overexpression, without modifying parasite burden in the organ. Cur was capable of blocking Ca2+-dependent NFATc1 transcriptional activity, COX-2 and mPGES-1 induction, and subsequent PGE2 production in ET-1-stimulated and parasite-infected cardiomyocytes. Furthermore, the decline of cardiomyocyte-derived prostaglandin levels achieved upon Cur treatment impaired effective PGE2/EP4 receptor interaction, resulting in attenuated expression of BNP, a strong indicator of cardiac pathogenesis in Chagas disease, in both infected and uninfected cells. Conclusion: Our current study shows a putative mechanism of action of Cur involving inhibition of the Ca2+/NFAT-dependent, pathogenic COX-2/mPGES-1/PGE2 pathway in T. cruzi-infected myocytes, underlying cardioprotection achieved in Cur-treated infected mice. With a view to the limited therapeutic possibilities available, Cur represents a promising approach for the treatment of Chagas heart disease
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Gmbh
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Curcumin
dc.subject
Trypanosoma Cruzi
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Cardiomyocyte
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Cyclooxygenase Type 2
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Prostaglandin E2
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B-Type Natriuretic Peptide
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Cardioprotective actions of curcumin on the pathogenic NFAT/COX-2/prostaglandin E2 pathway induced during Trypanosoma cruzi infection
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-05-31T14:40:04Z
dc.journal.volume
23
dc.journal.number
12
dc.journal.pagination
1392-1400
dc.journal.pais
Alemania
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dc.journal.ciudad
Stuttgart
dc.description.fil
Fil: Hernández, Matías. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: Wicz, Susana. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: Corral, Ricardo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
dc.journal.title
Phytomedicine
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.phymed.2016.06.017
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0944711316300988
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