Article Publish Status: FREE
Abstract Title:

Synergistic effect of the flavonoid catechin, quercetin, or epigallocatechin gallate with fluconazole induces apoptosis in Candida tropicalis resistant to fluconazole.

Abstract Source:

Antimicrob Agents Chemother. 2014 ;58(3):1468-78. Epub 2013 Dec 23. PMID: 24366745

Abstract Author(s):

Cecília Rocha da Silva, João Batista de Andrade Neto, Rosana de Sousa Campos, Narjara Silvestre Figueiredo, Letícia Serpa Sampaio, Hemerson Iury Ferreira Magalhães, Bruno Coêlho Cavalcanti, Danielle Macêdo Gaspar, Geanne Matos de Andrade, Iri Sandro Pampolha Lima, Glauce Socorro de Barros Viana, Manoel Odorico de Moraes, Marina Duarte Pinto Lobo, Thalles Barbosa Grangeiro, Hélio Vitoriano Nobre Júnior

Article Affiliation:

Cecília Rocha da Silva


Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (-)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation.

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