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

PLoS One. 2015 Mar 4;10(3):e0118932. doi: 10.1371/journal.pone.0118932. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology*
  • Benzoates / therapeutic use
  • Deferasirox
  • Hyphae / drug effects
  • Hyphae / growth & development
  • Immunomodulation / drug effects
  • Immunotherapy*
  • Iron / metabolism*
  • Iron / pharmacology
  • Iron Chelating Agents / pharmacology*
  • Iron Chelating Agents / therapeutic use
  • Pythiosis / drug therapy
  • Pythiosis / immunology
  • Pythiosis / therapy
  • Pythium / drug effects*
  • Pythium / growth & development*
  • Pythium / physiology
  • Rabbits
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Iron
  • Deferasirox

Grant support

This work was supported by the National Council for Scientific and Technological Development—CNPq (grant number 471114/2010-3 to SHA) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul—CAPES/FAPERGS (to RAZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.