TABLE 5.
Effects of buthionine sulfoximine on toxicity of nifurtimox and benznidazole against T. cruzi intracellular amastigotesa
| Drug concn (μM) | Nifurtimox
|
Benznidazole
|
||||||
|---|---|---|---|---|---|---|---|---|
| Infected Vero cells (%)
|
Endocytic index
|
Infected Vero cells (%)
|
Endocytic index
|
|||||
| Without BSO | With BSO (25 μM) | Without BSO | With BSO (25 μM) | Without BSO | With BSO (25 μM) | Without BSO | With BSO (25 μM) | |
| 0 | 32.4 ± 2.6 | 35.3 ± 2.8 | 5,505 ± 340 | 5,747 ± 359 | 29.0 ± 1.7 | 26.0 ± 1.6 | 5,787 ± 344 | 5,792 ± 347 |
| 0.5 | 27.0 ± 2.2 | 20.6 ± 1.7 | 2,494 ± 199 | 980 ± 78 | 17.7 ± 1.1 | 12.7 ± 0.8 | 4,015 ± 240 | 1,952 ± 117 |
| 1 | 24.3 ± 1.9 | 17.7 ± 1.4 | 802 ± 64 | 462 ± 69 | 15.8 ± 1.4 | 8.9 ± 0.5 | 2,356 ± 141 | 385 ± 23 |
Vero cells previously infected with MF trypomastigotes were incubated for 72 h in the presence or absence of benznidazole and nifurtimox alone or in combination with BSO. The culture medium with or without the drugs was changed every 24 h. At 72 h the total Vero cells, infected Vero cells, and number of amastigotes per Vero cell were determined by direct microscopic visualization, and the endocytic index was calculated as described in Materials and Methods. All values correspond to the means ± SD from three independent experiments. P values were <0.0001 from the two-way ANOVA for the percentage of infected Vero cells and the endocytic index with nifurtimox versus nifurtimox-BSO and benznidazole versus benznidazole-BSO treatments.