Dos Santos Fabiane Matos, Caldas Sérgio, de Assis Cáu Stêfany Bruno, Crepalde Geovam Pereira, de Lana Marta, Machado-Coelho George L L, Veloso Vanja Maria, Bahia Maria Terezinha
Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil.
Exp Parasitol. 2008 Dec;120(4):385-90. doi: 10.1016/j.exppara.2008.09.007. Epub 2008 Sep 14.
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.
通过持续的体内药物压力方案，以小鼠为实验模型，我们在克氏锥虫株中诱导出了对苯硝唑的抗性。在所分析的五株克氏锥虫中，有四株获得了完全抗性。然而，诱导抗性所需的苯硝唑剂量（40 - 180）以及时间（4 - 18个月）在不同的克氏锥虫株之间有所不同。在克氏锥虫株在小鼠体内传代12次（六个月）并在无细胞培养中培养相同时间后，抗性表型保持稳定。然而，抗性寄生虫在无细胞培养中维持12个月会导致其对苯硝唑的抗性水平降低，而在小鼠中维持相同时间的寄生虫未检测到变化。数据显示了通过药物压力获得的抗性的稳定性，但表明在无细胞培养中长时间维持后抗性水平可能发生可逆变化。
