Antineoplastic drug, carboplatin, protects mice against visceral leishmaniasis

Abstract

In the present study, the leishmanicidal effect of two doses (5 and 10mg/kg body weight) of the carboplatin was studied in Leishmania donovani-infected BALB/c mice. Mice were infected intracardially with promastigotes of L. donovani, and a month after infection, they were treated intraperitoneally with the two doses of the drug (5 and 10mg/kg body weight) for five continuous days. Animals were sacrificed on 1 and 15 posttreatment days. Hepatic parasite load was assessed on Geimsa-stained imprints. Immune responses were studied by measuring delayed-type hypersensitivity (DTH) responses, serum IgG isotype levels (IgG1 and IgG2a) and cytokine levels [γ-interferon (IFN-γ), interleukin (IL)-10 and IL-2] in spleen cell cultures by ELISA. To study the drug-induced side effects, various haematological (haemoglobin and total leukocyte count), biochemical (liver and kidney function tests) and histological investigations (kidney, liver and spleen) were carried out. The antileishmanial potential of the drug was revealed by significant reduction in the parasite burden. The infected and treated animals were also found to exhibit increased DTH responses, higher IgG2a levels, lower IgG1 levels and greater cytokine (IFN-γ, IL-10 and IL-2) concentrations pointing towards the generation of mixed Th1/Th2 response. Liver and kidney function tests and histological studies of kidney, liver and spleen of treated mice revealed no side effects. Carboplatin cures mice of visceral leishmaniasis without causing any serious side effects, and the drug was found be more effective at a dose of 10mg/kg body weight as compared to 5mg/kg body weight.