Benznidazole modulates release of inflammatory mediators by cardiac spheroids infected with Trypanosoma cruzi

dc.creatorFiuza, Ludmila Ferreira de Almeida
dc.creatorBatista, Denise da Gama Jaen
dc.creatorNunes, Daniela Ferreira
dc.creatorMoreira, Octacílio Cruz
dc.creatorCascabulho, Cynthia
dc.creatorSoeiro, Maria de Nazaré Correia
dc.date2021-07-17T19:24:33Z
dc.date2021-07-17T19:24:33Z
dc.date2021
dc.date.accessioned2023-09-27T00:11:14Z
dc.date.available2023-09-27T00:11:14Z
dc.identifierFIUZA, Ludmila Ferreira de Almeida et al. Benznidazole modulates release of inflammatory mediators by cardiac spheroids infected with Trypanosoma cruzi. Experimental Parasitology, v. 221, 108061, p. 1-6, 2021.
dc.identifier0014-4894
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/48268
dc.identifier10.1016/j.exppara.2020.108061
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898313
dc.descriptionChagas disease (CD) caused by Trypanosoma cruzi remains a serious public health problem in Latin America. The available treatment is limited to two old drugs, benznidazole (Bz) and nifurtimox, which exhibit limited efficacy and trigger side effects, justifying the search for new therapies. Also, more accurate and sensitive experimental protocols for drug discovery programs are necessary to shrink the translational gaps found among pre-clinical and clinical trials. Presently, cardiac spheroids were used to evaluate host cell cytotoxicity and anti-T.cruzi ac tivity of benznidazole, exploring its effect on the release of inflammatory mediators. Bz presented low toxic profile on 3D matrices (LC50 > 200 μM) and high potency in vitro (EC50 = 0.99 μM) evidenced by qPCR analysis of T.cruzi-infected cardiac spheroids. Flow cytometry appraisal of inflammatory mediators released at the cellular supernatant showed increases in IL - 6 and TNF contents (≈190 and ≈ 25-fold) in parasitized spheroids as compared to uninfected cultures. Bz at 10 μM suppressed parasite load (92%) concomitantly decreasing in IL-6 (36%) and TNF (68%). Our findings corroborate the successful use of 3D cardiac matrices for in vitro identifi cation of novel anti-parasitic agents and potential impact in host cell physiology.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectDoença de Chagas
dc.subjectTrypanosoma cruzi
dc.subjectBenznidazole
dc.subjectAvaliação Pré-Clínica de Medicamentos
dc.subjectMediadores inflamatórios
dc.subjectEsferoides cardíacos
dc.subjectChagas Disease
dc.subjectTrypanosoma cruzi
dc.subjectCardiac spheroids
dc.subjectDrug screening
dc.subjectBenznidazole
dc.subjectInflammatory mediators
dc.subjectAvaliação Pré-Clínica de Medicamentos
dc.titleBenznidazole modulates release of inflammatory mediators by cardiac spheroids infected with Trypanosoma cruzi
dc.typeArticle


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