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Efficacy of Ebselen Against Invasive Aspergillosis in a Murine Model.
Sakita, Karina Mayumi; Capoci, Isis Regina Grenier; Conrado, Pollyanna Cristina Vincenzi; Rodrigues-Vendramini, Franciele Abigail Vilugron; Faria, Daniella Renata; Arita, Glaucia Sayuri; Becker, Tânia Cristina Alexandrino; Bonfim-Mendonça, Patricia de Souza; Svidzinski, Terezinha Inez Estivalet; Kioshima, Erika Seki.
Affiliation
  • Sakita KM; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Capoci IRG; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Conrado PCV; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Rodrigues-Vendramini FAV; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Faria DR; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Arita GS; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Becker TCA; Laboratory of General Pathology, Department of Basic Health Sciences, State University of Maringá, Maringá, Brazil.
  • Bonfim-Mendonça PS; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Svidzinski TIE; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
  • Kioshima ES; Laboratory of Medical Mycology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Brazil.
Front Cell Infect Microbiol ; 11: 684525, 2021.
Article in En | MEDLINE | ID: mdl-34249777
ABSTRACT
Invasive aspergillosis is one of the major causes of morbidity and mortality among invasive fungal infections. The search for new antifungal drugs becomes imperative when existing drugs are not able to efficiently treat these infections. Ebselen, is an organoselenium compound, already successfully approved in clinical trials as a repositioned drug for the treatment of bipolar disorder and prevention of noise-induced hearing loss. In this study, we aimed to reposition ebselen for the treatment of invasive aspergillosis by showing ebselen effectiveness in a murine model. For this, BALB/c mice were immunosuppressed and infected systemically with Aspergillus fumigatus. Animals were divided and treated with ebselen, voriconazole, or drug-free control, for four days. The kidneys were used for CFU count and, histopathological and cytokine analysis. Ebselen was able to significantly reduce the fungal burden in the kidneys of infected mice with efficacy comparable with voriconazole treatment as both had reductions to the same extent. The absence of hyphae and intact kidney tissue structure observed in the histopathological sections analyzed from treated groups corroborate with the downregulation of IL-6 and TNF. In summary, this study brings for the first time in vivo evidence of ebselen efficacy against invasive aspergillosis. Despite these promising results, more animal studies are warranted to evaluate the potential role of ebselen as an alternative option for the management of invasive aspergillosis in humans.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aspergillosis / Invasive Fungal Infections Limits: Animals Language: En Journal: Front Cell Infect Microbiol Year: 2021 Document type: Article Affiliation country: Brazil

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aspergillosis / Invasive Fungal Infections Limits: Animals Language: En Journal: Front Cell Infect Microbiol Year: 2021 Document type: Article Affiliation country: Brazil