Journal
EXPERIMENTAL PARASITOLOGY
Volume 120, Issue 4, Pages 385-390Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2008.09.007
Keywords
Trypanosoma cruzi; Drug resistance; Chemotherapy
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Funding
- Universidade Federal de Ouro Preto (UFOP)
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais [FAPEMIG-CBB 538/03]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [CNPq-478.799/03 8]
- CNPq
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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. (C) 2008 Elsevier Inc. All rights reserved.
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