Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice

• Published in: Experimental parasitology Vol. 120; no. 4; pp. 314 - 319
• Main Authors: Francisco, Amanda Fortes, de Abreu Vieira, Paula Melo, Arantes, Jerusa Marilda, Pedrosa, Maria Lúcia, Martins, Helen Rodrigues, Silva, Maisa, Veloso, Vanja Maria, de Lana, Marta, Bahia, Maria Terezinha, Tafuri, Washington Luiz, Carneiro, Cláudia Martins
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2008; Elsevier
• Subjects: Analysis of Variance; Analysis of variance (ANOVA); Animals; benznidazole (BZ); Biological and medical sciences; Chagas Disease - drug therapy; Chagas Disease - mortality; Chagas’ disease (CD); Days post-infection (dpi); Deferoxamine - pharmacology; Deferoxamine - therapeutic use; Deoxyribonucleic acid (DNA); desferrioxamine (DFO); Disease Models, Animal; Drug Therapy, Combination; Ethylenediamine tetraacetic acid (EDTA); Fundamental and applied biological sciences. Psychology; Hemoglobins - analysis; Intraperitoneal (ip); Iron - analysis; Iron - blood; Iron - metabolism; Life cycle. Host-agent relationship. Pathogenesis; Liver - chemistry; Liver - drug effects; Liver infusion tryptose (LIT); Male; Mice; Nitroimidazoles - pharmacology; Nitroimidazoles - therapeutic use; Parasitemia - drug therapy; Parasitemia - mortality; Polymerase Chain Reaction; Polymerase chain reaction (PCR); Protozoa; Random Allocation; Reactive oxygen species (ROS); Siderophores - pharmacology; Siderophores - therapeutic use; Trypanocidal Agents - pharmacology; Trypanocidal Agents - therapeutic use; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Deoxyribonucleic acid (DNA); Liver infusion tryptose (LIT); desferrioxamine (DFO); benznidazole (BZ); Polymerase chain reaction (PCR); Reactive oxygen species (ROS); Analysis of variance (ANOVA); Intraperitoneal (ip); Ethylenediamine tetraacetic acid (EDTA); Chagas’ disease (CD); Days post-infection (dpi); Trypanosoma cruzi; Oxidative stress; Protozoal disease; Benznidazole; Liver; Chagas disease; Iron; Free radical; Deferoxamine; Intraperitoneal; Infusion; Chagas' disease (CD); Trypanosomiasis; Kinetoplastida; Protozoa; Cadmium; Rodentia; Parasite; Parasitosis; Variance analysis; Infection; Polymerase chain reaction; Vertebrata; Mammalia; Mouse; DNA
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2008.08.002

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.