Table 2.
The activity of L. donovani parasites with different inherent Sb susceptibilities which had induced resistance to Milt, i.e., Milt-Sb-sensitive, Milt-Sb-intermediate or Milt-Sb-resistant, at the promastigotes and intracellular amastigotes stage. The activity of APCs against bone-derived macrophages or L. donovani parasites with different inherent susceptibilities to antimony, i.e., Sb-sensitive, Sb-intermediate or Sb-resistant, at the promastigotes and intracellular amastigotes stage was determined. Bone-marrow-derived macrophages from BALB/c mice (x/mL), L. donovani promastigotes (x/mL) or macrophages infected with L. donovani promastigotes for 24 h were cultured with medium alone (controls) or different concentrations of APCs for 3 days (n = 3/treatment). The cytotoxicity of the APCs against uninfected macrophages was determined using an alamar blue colorimetric assay assay whereas a luciferase assay was used for parasite studies. The suppression in uninfected macrophage or parasite survival was determined by comparing individual experimental values with the relevant mean control data. These values were used to determine the mean IC50, using the Grafit software, Cross Resistance Index (CRI50) and Selectivity index (SI50) shown.
| Strain | Antimony Resistance | Drug | Mean IC50 µg/mL (µM) | Promast: Amast Ratio | Cross-Resistance Index (CRI50) (Promast/Amast) |
Selectivity Index (SI50) | |
|---|---|---|---|---|---|---|---|
| Promastigotes | Amastigotes | ||||||
| 282/4 | Sb-sensitive | APC12 | ** 0.55 ± 0.02 (1.56 ± 0.06) |
** 0.26 ± 0.01 (0.74 ± 0.03) |
2.09 | NA/NA | 136.08 |
| APC14 | ** 0.44 ± 0.07 (1.16 ± 0.18) |
** 0.12 ± 0.02 (0.32 ± 0.05) |
3.64 | NA/NA | 340.75 | ||
| APC16 | 0.84 ± 0.05 (2.06 ± 0.12) |
0.31 ± 0.02 (0.76 ± 0.05) |
2.68 | NA/NA | 16.39 | ||
| 087/11 | Sb-intermediate | APC12 | ** 0.42 ± 0.02 (1.19 ± 0.06) |
** 0.20 ± 0.07 (0.57 ± 0.20) |
2.11 | 0.76/0.77 | 176.90 |
| APC14 | ** 0.21 ± 0.00 (0.55 ± 0.00) |
** 0.19 ± 0.01 (0.50 ± 0.03) |
1.05 | 0.48/1.58 | 215.21 | ||
| APC16 | 1.49 ± 0.6 (3.66 ± 1.47) |
0.29 ± 0.01 (0.71 ± 0.02) |
5.15 | 1.77/1.76 | 17.52 | ||
| 275/18 | Sb-resistant | APC12 | ** 0.49 ± 0.03 (1.39 ± 0.09) |
** 0.23 ± 0.01 (0.65 ± 0.03) |
2.10 | 0.89/0.88 | 153.83 |
| APC14 | ** 0.37 ± 0.05 (0.97 ± 0.13) |
** 0.28 ± 0.00 (0.74 ± 0.00) |
1.31 | 0.84/2.33 | 146.04 | ||
| APC16 | 1.26 ± 0.06 (3.09 ± 0.15) |
0.51 ± 0.00 (1.25 ± 0.00) |
2.49 | 1.50/1.65 | 9.96 | ||
* p < 0.05, ** p < 0.01 compared to APC16. NA Data not available.