Complex interaction of deferasirox and Pythium insidiosum: iron-dependent attenuation of growth in vitro and immunotherapy-like enhancement of immune responses in vivo

Pythium insidiosum iron acquisition mechanisms are unknown. We previously showed that the iron chelator deferasirox had weak activity in vitro and in rabbits with experimental pythiosis. Here we show that deferasirox causes damage to P. insidiosum hyphae in vitro, but that activity is diminished in...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0118932-e0118932
Main Authors: Zanette, Régis A, Bitencourt, Paula E R, Kontoyiannis, Dimitrios P, Fighera, Rafael A, Flores, Mariana M, Kommers, Glaucia D, Silva, Priscila S, Ludwig, Aline, Moretto, Maria B, Alves, Sydney H, Santurio, Janio M
Format: Article
Language:English
Subjects:
Adenosine
Adenosine deaminase
Animals
Benzoates - pharmacology
Benzoates - therapeutic use
Care and treatment
Complications and side effects
Deferasirox
Dendritic cells
Diagnosis
Dosage and administration
Health aspects
Histopathology
Hyphae
Hyphae - drug effects
Hyphae - growth & development
Immune response
Immunomodulation - drug effects
Immunotherapy
Infections
Inflammation
Iron
Iron - metabolism
Iron - pharmacology
Iron Chelating Agents - pharmacology
Iron Chelating Agents - therapeutic use
Lesions
Mucorales
Patient outcomes
Pharmaceutical sciences
Pharmacology
Pythiosis - drug therapy
Pythiosis - immunology
Pythiosis - therapy
Pythium
Pythium - drug effects
Pythium - growth & development
Pythium - physiology
Rabbits
Triazoles - pharmacology
Triazoles - therapeutic use
Veterinary medicine
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Summary:Pythium insidiosum iron acquisition mechanisms are unknown. We previously showed that the iron chelator deferasirox had weak activity in vitro and in rabbits with experimental pythiosis. Here we show that deferasirox causes damage to P. insidiosum hyphae in vitro, but that activity is diminished in the presence of exogenous iron. The tissue activity of the proinflammatory enzyme adenosine deaminase and the histological pattern observed in pythiosis lesions of rabbits treated with deferasirox were similar to the ones in animals treated with immunotherapy.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0118932