TABLE 1.
Bioluminescence signal and lesion suppression rates in BALB/c mice treated with known antileishmanial compoundsa
| Compound tested | Dose (mg/kg) | Bioluminescence signal suppression at 18 ± 1 days postinfection | Lesion suppression at 60 ± 2 days postinfection |
|---|---|---|---|
| Amphotericin B formulations | |||
| Amphotericin B | 2 | −88.1 | −70.7 |
| Amphotericin B | 4 | −150.0 | −33.0 |
| Amphotericin B | 6 | 36.5 | 66.7 |
| Amphotericin B | 8 | 67.3* | 88.8* |
| Amphotericin B | 16 | 99.1* | 84.5* |
| ABLC | 12.5 | 74.2* | 60.9* |
| ABLC | 25 | 93.1* | 77.9* |
| ABLC | 37.5 | 99.4* | 96.5* |
| AmBisome | 12.5 | 99.4* | 80.7* |
| AmBisome | 25 | 99.8* | 99.1* |
| AmBisome | 37.5 | 100* | 100.0* |
| AmBisome | 50 | 100* | 100.0* |
| Other antileishmanial compounds | |||
| Paromomycin | 80 | 100* | 100* |
| Sodium stibogluconate | 400 | 89.7* | 65.9 |
| Pentamidine | 50 | 68.9 | 63.1& |
| Sinefungin | 10b | 99.9* | Euthanized |
| Posaconazole | 100 | 94.9* | 96.5* |
| Ofloxacin | 80 | −52.8 | −85.4 |
| Miltefosine | 17.5 | 18.1 | −20.1 |
| Fluconazole | 160 | −0.4 | −10.6 |
| Glucantime | 100 | −13.7 | −29.8 |
The lesion suppression activities of different doses of the three formulations of amphotericin B and other known antileishmanial compounds are shown. Five BALB/c mice were assigned to each treatment and vehicle-control group. Mice were infected i.d. with 1 × 107 stationary-phase luciferase-expressing L. major parasites at the base of the tail on day 0. Drug treatments were initiated on day 3 postinfection. Drugs were given for 10 consecutive days, except for paromomycin, sodium stibogluconate, sinefungin, and i.m. pentamidine, which were given for 7, 14, 8, and 3 days, respectively. The mean bioluminescence signals at the infection site (in number of photons per second per mouse) and the mean lesion size (in square millimeters) were measured on days 18 ± 1 and 60 ± 2 postinfection, respectively, and were expressed as a percentage of the bioluminescence signal compared with that for the vehicle-control group or the mean percent lesion suppression compared with that for the vehicle-control group. A single-factor ANOVA (Dunnett's test) was used to determine whether differences in group means existed across the experiment. *, a statistically significant difference (P < 0.05); &, lesion size was last measured on day 33 postinfection.
The bioluminescence signal was measured for the last time on day 11 postinfection, when all animals were euthanized due to drug toxicity (weight loss, ≥20%). As a result, only eight doses of sinefungin were given.