Trypanosoma cruzi: effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice.
Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the development of infection in mice inoculated with Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy.
Francisco
Amanda Fortes
AF
Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Rua Costa Sena, 171, Campus Universitário Morro do Cruzeiro Cep: 35 400-000 Ouro Preto, MG, Brazil.
de Abreu Vieira
Paula Melo
PM
Arantes
Jerusa Marilda
JM
Pedrosa
Maria Lúcia
ML
Martins
Helen Rodrigues
HR
Silva
Maisa
M
Veloso
Vanja Maria
VM
de Lana
Marta
M
Bahia
Maria Terezinha
MT
Tafuri
Washington Luiz
WL
Carneiro
Cláudia Martins
CM
D000704:Analysis of Variance; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000401:mortality; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006454:Hemoglobins / Q000032:analysis; D007501:Iron / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018512:Parasitemia / Q000188:drug therapy / Q000401:mortality; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
D006454:Hemoglobins; D009593:Nitroimidazoles; D017262:Siderophores; D014344:Trypanocidal Agents; D007501:Iron; D003676:Deferoxamine; C009999:benzonidazole