In-vitro and In-vivo Antileishmanial Activity of a Compound Derived of Platinum, Oxaliplatin, against Leishmania Major.

Abstract

This study aimed to evaluate the antileishmanial efficacy of oxaliplatin against Leishmania major (L. major) both in-vitro and in-vivo. The IC50, CC50, and SI of oxaliplatin against promastigotes, murine macrophages, Raw 264.7 cells, and intramacrophage amastigotes of L. major were investigated in-vitro. The effects of this drug on intracellular amastigotes were also assayed, and the percentage of infectivity and IIR were calculated. Flow cytometry was performed to assay apoptosis, using 50 and 100 µg/mL of oxaliplatin in the promastigotes and macrophages. In-vivo, the BALB/c mice were classified into three groups, receiving oxaliplatin, glucantime, and phosphate-buffered saline for one month, respectively. The lesion size, IFN-γ, and IL-4 levels, and parasite burden were also evaluated in the animals. After 72 h, the IC50 and CC50 of oxaliplatin against promastigotes and macrophages were respectively 0.5 and 66.78 µg/mL. The apoptosis of promastigotes and macrophages using 50 µg/mL of oxaliplatin was 7.25% and 2.14%, respectively, while apoptosis induced at 100 µg/mL was 15.48% and 2.80%, respectively. Similar to the glucantime group, the mice treated with oxaliplatin showed a lower parasite burden and smaller lesions, compared with the PBS group (p < 0.01). Furthermore, higher IFN-γ levels were reported in mice receiving oxaliplatin in comparison with those receiving PBS (p < 0.01). The current findings indicated the efficacy of oxaliplatin against promastigote and amastigote forms of Leishmania and L. major-induced leishmaniasis.