Abstract
The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated that the diminazene–chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene–chloroquine combination was safer (Ld50 = 0.03±0.04) than Amphotericin B (Ld50 = 0.02±0.01). Body weight in infected mice increased significantly (P = 0.0007) from day 7 to day 37 following infection (P = 0.026). However, body weight remained comparable in all mice groups during treatment (P = 0.16). The diminazene–chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies (P = 0.0001) although Amphotericin B was still more efficacious than any other treatment (P = 0.0001). Amongst the test compounds, the diminazene–chloroquine combination showed the lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial antibody responses and protection against disease. These findings demonstrate the positive advantage and the potential use of a combined therapy of diminazene–chloroquine over the constituent drugs. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.
Highlights
Visceral leishmaniasis (VL), known as Kalaazar, is a protozoan systemic infection, which is always fatal if left untreated[1]
The present study investigated the protective potential of diminazene (Dim) combined with chloroquine (Chq) compounds in BALB/c mice experimentally infected with L. donovani
As part of the efforts to develop safe and effective drug against leishmaniasis, the present study evaluated the in vitro safety and efficacy of this drug against Leishmania donovani promastigotes as well as the effects of the drug combination of visceral leishmaniasis in the murine system
Summary
Visceral leishmaniasis (VL), known as Kalaazar, is a protozoan systemic infection, which is always fatal if left untreated[1]. There is currently no vaccine against any form of leishmaniasis in routine use anywhere in the world[3] Vector control measures, such as residual insecticide spraying and the use of insecticide-treated bed nets or curtains may offer effective protection[4]. A recent study has tested the synergistic effects of diminazene and artesunate (an anti-malarial drug) against murine visceral leishmaniasis and the results pointed to a potential application of this drug combination against leishmaniasis[5]. Chloroquine has, since accrued a plethora of uses in the treatment and amelioration of several other diseases and conditions because of its lysosomotropic properties[10] It has characteristic physiological and systemic effects. The present study investigated the protective potential of diminazene (Dim) combined with chloroquine (Chq) compounds in BALB/c mice experimentally infected with L. donovani. The in vitro safety and efficacy of the drug combination were evaluated
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