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 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.
Graduate Program in Pharmacology, Health Science Center, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil.
Régis A
RA
Zanette
Graduate Program in Pharmaceutical Sciences, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Paula E R
PE
Bitencourt
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Dimitrios P
DP
Kontoyiannis
Graduate Program in Veterinary Medicine, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Rafael A
RA
Fighera
Graduate Program in Veterinary Medicine, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Mariana M
MM
Flores
Graduate Program in Veterinary Medicine, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Glaucia D
GD
Kommers
Graduate Program in Pharmaceutical Sciences, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Priscila S
PS
Silva
Graduate Program in Pharmacology, Health Science Center, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil.
Aline
A
Ludwig
Graduate Program in Pharmaceutical Sciences, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Maria B
MB
Moretto
Graduate Program in Pharmacology, Health Science Center, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil; Graduate Program in Pharmaceutical Sciences, Health Science Center, UFSM, Santa Maria, RS, Brazil.
Sydney H
SH
Alves
Graduate Program in Pharmacology, Health Science Center, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil.
Janio M
JM
Santurio
D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D000077588:Deferasirox; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D058968:Pythiosis / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D011775:Pythium / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D011817:Rabbits; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox