title: Iron chelation therapy as a treatment for Pythium insidiosum in an animal model.
abstract: OBJECTIVE
  Iron plays an important role in the pathogenesis of Pythium insidiosum. Human pythiosis frequently occurs in iron-overloaded thalassaemic patients and experimentally infected animals develop iron deficiency anaemia. Therefore, we sought to determine the in vitro and in vivo activities of the iron chelator deferasirox against P. insidiosum.
  
  
  METHODS
  In vitro, the MIC and minimum fungicidal concentration (MFC) values of deferasirox for 17 strains of P. insidiosum were determined in accordance with CLSI document M38-A2. In vivo studies were carried out in 20 inoculated rabbits divided into four groups: placebo, immunotherapy obtained from vortexed P. insidiosum cultures (14 day intervals), deferasirox (15 mg/kg/day) and a combination of immunotherapy and deferasirox. Five non-infected animals were used as controls.
  
  
  RESULTS
  The MIC and MFC values of deferasirox for P. insidiosum ranged from 12.5 to 50 mg/L and from 50 to 100 mg/L, respectively. Treatment with deferasirox alone ameliorated anaemia and normalized the serum iron levels and hepatic iron concentration in the animals. However, the mean lesion size, although decreased, did not differ significantly from that in the placebo group. The results of immunotherapy plus iron chelation therapy were worse than those of immunotherapy alone. Moreover, the disease spread to the lung tissue in 5 out of 10 deferasirox-treated animals.
  
  
  CONCLUSIONS
  Despite its limited in vitro and in vivo activity, deferasirox improved iron deficiency anaemia in P. insidiosum-infected rabbits. Further studies are needed to investigate the immunomodulatory properties observed in this study and the benefits and drawbacks of using iron-chelating drugs as an adjuvant therapy in pythiosis.
authors: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: R A
authors: RA
authors: Zanette
authors: S H
authors: SH
authors: Alves
authors: M B
authors: MB
authors: Pilotto
authors: C
authors: C
authors: Weiblen
authors: R A
authors: RA
authors: Fighera
authors: P
authors: P
authors: Wolkmer
authors: M M
authors: MM
authors: Flores
authors: J M
authors: JM
authors: Santurio
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage*; D015913:Chelation Therapy / Q000379:methods*; D000077588:Deferasirox; D005260:Female; D007167:Immunotherapy / Q000379:methods; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D058968:Pythiosis / Q000188:drug therapy*; D011775:Pythium / Q000187:drug effects / Q000302:isolation & purification*; D011817:Rabbits; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000908:Antibodies, Fungal; D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox