title: Concomitant Benznidazole and Suramin Chemotherapy in Mice Infected with a Virulent Strain of Trypanosoma cruzi.
abstract: Although suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Eliziária C
authors.initials: EC
authors.lastname: Santos
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil Department of Biological Sciences and NUPEB, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil romuonovaes@yahoo.com.br leandro.licursi@ufv.br.
authors.forename: Rômulo D
authors.initials: RD
authors.lastname: Novaes
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Marli C
authors.initials: MC
authors.lastname: Cupertino
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Daniel S S
authors.initials: DS
authors.lastname: Bastos
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Raphael C
authors.initials: RC
authors.lastname: Klein
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Eduardo A M
authors.initials: EA
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
authors.forename: Juliana L R
authors.initials: JL
authors.lastname: Fietto
authors.affiliation: Department of Biological Sciences and NUPEB, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.affiliation: Department of Biological Sciences and NUPEB, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Bahia
authors.affiliation: Departament of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil romuonovaes@yahoo.com.br leandro.licursi@ufv.br.
authors.forename: Leandro L
authors.initials: LL
authors.lastname: Oliveira
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000469:parasitology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D059208:Parasite Load; D013498:Suramin / Q000009:adverse effects*; D016019:Survival Analysis; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; D013498:Suramin; D007371:Interferon-gamma; C009999:benzonidazole