| Revista: | Memorias do Instituto Oswaldo Cruz |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000420036 |
| ISSN: | 0074-0276 |
| Autores: | Hernández, Matías1 Wicz, Susana1 Santamaría, Miguel H2 Corral, Ricardo S3 |
| Instituciones: | 1Universidad Nacional de San Luis, Facultad de Química, Bioquímica y Farmacia, San Luis. Argentina 2Centro de Estudios Metabólicos, Laboratorio de Biología Experimental, Santander, Cantabria. España 3Hospital de Niños "Dr. Ricardo Gutiérrez", Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas, Buenos Aires. Argentina |
| Año: | 2018 |
| Volumen: | 113 |
| Número: | 9 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | 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 |
| Disciplinas: | Medicina |
| Palabras clave: | Farmacología, Parasitología, Enfermedad de Chagas, Infección experimental, Actividad antiinflamatoria, Cardioprotección, Flavonoides, Curcumina, Curcuma longa, Zingiberaceae |
| Keyword: | Pharmacology, Parasitology, Chagas disease, Experimental infection, Antiinflammatory activity, Cardioprotection, Flavonoids, Curcumin, Curcuma longa, Zingiberaceae |
| Texto completo: | Texto completo (Ver HTML) |
