title: Trypanosoma cruzi: Induction of benznidazole resistance in vivo and its modulation by in vitro culturing and mice infection.
abstract: Through a continuous in vivo drug pressure protocol, using mice as experimental model, we induced benznidazole resistance in Trypanosoma cruzi stocks. Full resistance was obtained for four out of five T. cruzi stocks analyzed. However, the number of benznidazole doses (40-180), as well as the time (4-18 months) necessary to induce resistance varied among the different T. cruzi stocks. The resistance phenotype remained stable after T. cruzi stocks has been maintained by 12 passages in mice (six months) and in acellular culture for the same time. However, the maintenance of resistant parasite for 12 months in acellular culture induces a reduction in its level of benznidazole resistance, while no alteration was detected in parasite maintained for the same time in mice. The data showed the stability of the resistance acquired by drug pressure, but suggest the possibility of reversible changes in the resistance levels after maintenance for long time in acellular culture.
authors.affiliation: Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Fabiane Matos
authors.initials: FM
authors.lastname: Dos Santos
authors.forename: Sérgio
authors.initials: S
authors.lastname: Caldas
authors.forename: Stêfany Bruno
authors.initials: SB
authors.lastname: de Assis Cáu
authors.forename: Geovam Pereira
authors.initials: GP
authors.lastname: Crepalde
authors.forename: Marta
authors.initials: M
authors.lastname: de Lana
authors.forename: George L L
authors.initials: GL
authors.lastname: Machado-Coelho
authors.forename: Vanja Maria
authors.initials: VM
authors.lastname: Veloso
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004285:Dogs; D004351:Drug Resistance; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D003520:Cyclophosphamide; C009999:benzonidazole