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

Chagas 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 activity 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 identification of novel anti-parasitic agents and potential impact in host cell physiology. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Ludmila Ferreira de Almeida Fiuza, Denise da Gama Jaen Batista, Daniela Ferreira Nunes, Otacílio Cruz Moreira, Cynthia Cascabulho, Maria de Nazaré Correia Soeiro. Benznidazole modulates release of inflammatory mediators by cardiac spheroids infected with Trypanosoma cruzi. Experimental parasitology. 2021 Feb;221:108061

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PMID: 33383023

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