title: Ruthenium complex with benznidazole and nitric oxide as a new candidate for the treatment of chagas disease.
abstract: BACKGROUND
  Chagas disease remains a serious medical and social problem in Latin America and is an emerging concern in nonendemic countries as a result of population movement, transfusion of infected blood or organs and congenital transmission. The current treatment of infected patients is unsatisfactory due to strain-specific drug resistance and the side effects of the current medications. For this reason, the discovery of safer and more effective chemotherapy is mandatory for the successful treatment and future eradication of Chagas disease.
  
  
  RESULTS
  We investigated the effect of a ruthenium complex with benznidazole and nitric oxide (RuBzNO2) against Trypanosoma cruzi both in vitro and in vivo. Our results demonstrated that RuBzNO2 was more effective than the same concentrations of benznidazole (Bz) in eliminating both the extracellular trypomastigote and the intracellular amastigote forms of the parasite, with no cytotoxic effect in mouse cells. In vivo treatment with the compound improved the survival of infected mice, inhibiting heart damage more efficiently than Bz alone. Accordingly, tissue inflammation and parasitism was significantly diminished after treatment with RuBzNO2 in a more effective manner than that with the same concentrations of Bz.
  
  
  CONCLUSIONS
  The complexation of Bz with ruthenium and nitric oxide (RuBzNO2) increases its effectiveness against T. cruzi and enables treatment with lower concentrations of the compound, which may reduce the side effects of Bz. Our findings provide a new potential candidate for the treatment of Chagas disease.
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Sesti-Costa
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Zumira A
authors.initials: ZA
authors.lastname: Carneiro
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Silva
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maíta
authors.initials: M
authors.lastname: Santos
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, São Paulo, Brazil.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Silva
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Milanezi
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: da Silva
authors.affiliation: Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, São Paulo, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000009:adverse effects / Q000494:pharmacology*; D018512:Parasitemia / Q000188:drug therapy; D012428:Ruthenium / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009569:Nitric Oxide; D012428:Ruthenium; C009999:benzonidazole