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Curcumin exerts anti-inflammatory and vasoprotective effects through amelioration of NFAT-dependent endothelin-1 production in mice with acute Chagas cardiomyopathy
Hernández, Matías; Wicz, Susana; Santamaría, Miguel H; Corral, Ricardo S.
  • Hernández, Matías; Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Laboratorio de Biomedicina Molecular. San Luis. AR
  • Wicz, Susana; Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Laboratorio de Biomedicina Molecular. San Luis. AR
  • Santamaría, Miguel H; Centro de Estudios Metabólicos. Laboratorio de Biología Experimental. Santander. ES
  • Corral, Ricardo S; Hospital de Niños Dr Ricardo Gutiérrez. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Servicio de Parasitología-Chagas. Ciudad Autónoma de Buenos Aires. AR
Mem. Inst. Oswaldo Cruz ; 113(9): e180171, 2018. graf
Article in English | LILACS | ID: biblio-955120
ABSTRACT
BACKGROUND The anti-inflammatory and cardioprotective properties of curcumin (Cur), a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa, are increasingly considered to have beneficial effects on the progression of Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi. OBJECTIVE To evaluate the effects of oral therapy with Cur on T. cruzi-mediated cardiovasculopathy in acutely infected mice and analyse the in vitro response of parasite-infected human microvascular endothelial cells treated with this phytochemical. METHODS Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial ET-1, IL-6, and TNF-α mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected in vitro with or without addition of Cur or Bz. Induction of the Ca2+/NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay. FINDINGS Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of IL-6/TNF-α (p < 0.01) and ET-1 (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 μM) interfered with T. cruzi-dependent activation of the Ca2+/NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells. CONCLUSIONS Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca2+/NFATc1-regulated release of ET-1 from T. cruzi-infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease.
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Full text: Available Index: LILACS (Americas) Main subject: Chagas Cardiomyopathy / Reverse Transcriptase Polymerase Chain Reaction / NFATC Transcription Factors Type of study: Prognostic study Limits: Humans Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2018 Type: Article Affiliation country: Argentina / Spain Institution/Affiliation country: Centro de Estudios Metabólicos/ES / Hospital de Niños Dr Ricardo Gutiérrez/AR / Universidad Nacional de San Luis/AR

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Full text: Available Index: LILACS (Americas) Main subject: Chagas Cardiomyopathy / Reverse Transcriptase Polymerase Chain Reaction / NFATC Transcription Factors Type of study: Prognostic study Limits: Humans Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2018 Type: Article Affiliation country: Argentina / Spain Institution/Affiliation country: Centro de Estudios Metabólicos/ES / Hospital de Niños Dr Ricardo Gutiérrez/AR / Universidad Nacional de San Luis/AR