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Oxidative damage by 1,10-phenanthroline-5,6-dione and its silver and copper complexes lead to apoptotic-like death in Trichomonas vaginalis.
Vargas Rigo, Graziela; Willig, Júlia Biz; Devereux, Michael; McCann, Malachy; Souza Dos Santos, André Luis; Tasca, Tiana.
Affiliation
  • Vargas Rigo G; Faculdade de Farmácia e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Willig JB; Laboratório de Análises Bioquímicas e Citológicas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Devereux M; The Centre for Biomimetic and Therapeutic Research, Focas Research Institute, Technological University Dublin, Dublin, Ireland.
  • McCann M; Chemistry Department, Maynooth University, National University of Ireland, Maynooth, Ireland.
  • Souza Dos Santos AL; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
  • Tasca T; Faculdade de Farmácia e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: tiana.tasca@ufrgs.br.
Res Microbiol ; 174(4): 104015, 2023 May.
Article in En | MEDLINE | ID: mdl-36566772
Trichomoniasis is a neglected, parasitic, sexually transmitted infection. Resistance to the only approved drugs is increasing worldwide, leaving millions of people without alternative medications. Thus, the search for new therapeutic options against this infection is necessary. Previously, our group reported that 1,10-phenanthroline-5,6-dione (phendione) and its silver(I) and copper (II) complexes (abbreviated as Ag-phendione and Cu-phendione, respectively) presented activity against the amitochondriate parasite T. vaginalis, with Cu-phendione being the most effective (IC50 = 0.84 µM). Methods: qRT-PCR, SEM, flow cytometry. The current study on the effects of Cu-phendione on the antioxidant metabolism of T. vaginalis by qRT-PCR revealed that the complex causes a decrease in the relative expression of mRNA of NADH oxidase, flavin reductase, superoxide dismutase, peroxiredoxin, iron-sulfur flavoprotein, rubrerythrin and osmotically inducible proteins. In contrast, the mRNA expression of flavodiiron protein was increased. Detoxification-related enzymes were downregulated, impairing oxygen metabolism in trophozoites and triggering a subsequent accumulation of the superoxide anion. Although no DNA fragmentation was observed, the treatment of parasites with Cu-phendione led to a significant reduction in cell size and a concomitant increase in granularity. The complex promoted phosphatidylserine exposure at the plasma membrane (as judged by Annexin V binding) and propidium iodide was unable to passively permeate the parasites. All of these outcomes are classical hallmarks of cell death by apoptosis. In essence, the trichomonacidal effect of Cu-phendione operates through redox homeostasis imbalance, which is a mode of action that is quite distinct from that caused by metronidazole.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichomonas vaginalis Limits: Humans Language: En Journal: Res Microbiol Journal subject: MICROBIOLOGIA Year: 2023 Document type: Article Affiliation country: Brazil Country of publication: France

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trichomonas vaginalis Limits: Humans Language: En Journal: Res Microbiol Journal subject: MICROBIOLOGIA Year: 2023 Document type: Article Affiliation country: Brazil Country of publication: France