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Amlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi Infection. | LitMetric

Amlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi Infection.

Antimicrob Agents Chemother

Laboratório de Parasitologia Básica, Programa de Pós-Graduação em Ciências Biológicas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, Brazil

Published: July 2020

AI Article Synopsis

Article Abstract

Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon experimental infection. assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (sum of the fractional inhibitory concentration [ΣFIC] > 0.5) of the combined treatment without additional toxicity to host cells. experiments, using a murine model of the Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the antiparasitic activity of underdosing ravuconazole regimens. Additional analysis using long-term treatment (20 days) showed that parasitemia relapse until 60 days after treatment was significatively lower in mice treated with the combination (4 out of 14 mice) than ravuconazole monotherapy (10 out of 14 mice), even in the presence of immunosuppressant pressure. Furthermore, the combined therapy was well tolerated and protected the mice from mortality. The treatments also impacted on the cellular and humoral immune response of infected animals, inducing a reduction of serum cytokine levels in all ravuconazole-treated mice. Our findings demonstrate that amlodipine is efficacious in enhancing the antiparasitic activity of ravuconazole in an experimental model of infection and indicates a potential strategy to be explored in Chagas disease treatment.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526806PMC
http://dx.doi.org/10.1128/AAC.02497-19DOI Listing

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