Abstract
Leishmaniasis, as a tropical and subtropical disease, is endemic in more than 90 countries around the world. Today, cutaneous leishmaniasis (CL) that affects more than 1.5 million people per year lacks a definitive treatment approach. Imatinib is an anticancer drug that inhibits the abnormal function of Bcr-Abl due to its tyrosine kinase inhibitor, and that was the reason why the drug was tested for CL treatment because protein kinases are essential enzymes in the Leishmania genus. In this study, the L. major CL model of Balb/c mice was produced by injection of the cultured metacyclic form of parasite at the base of the tail. The possible recovery of CL ulcers and determination of the optimum dose of imatinib against Leishmania amastigotes were evaluated. A significant decrease was observed in mice treated with amphotericin B (positive control group) as well as imatinib 50 mg/kg compared to the unreceived drug, negative control group (P<0.05). This study could be promising in gaining insight into the potential of imatinib as an effective treatment approach against CL.
Highlights
Leishmaniasis is a vector-borne protozoan disease caused by an obligatory intra-macrophage parasite of the genus Leishmania, which threatens 350 million people in more than 90 countries [1,2]
Imatinib is an anticancer drug that inhibits the abnormal function of Bcr-Abl due to its tyrosine kinase inhibitor, and that was the reason why the drug was tested for cutaneous leishmaniasis (CL) treatment because protein kinases are essential enzymes in the Leishmania genus
Few choice drugs are available for CL treatment to include pentavalent antimony compounds, sodium stibogluconate and meglumine antimoniate; none of them are efficient due to long course treatment and high toxicity as well as drug resistance reported among different species of Leishmania [10,11]
Summary
Leishmaniasis is a vector-borne protozoan disease caused by an obligatory intra-macrophage parasite of the genus Leishmania, which threatens 350 million people in more than 90 countries [1,2]. Imatinib is a small molecule kinase inhibitor (Figure). Imatinib is a small molecule kinase inhibitor (Figure1) It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs), and several other malignancies [12]. Protein kinases are critical enzymes for the survival of Leishmania species [13,14]. It is demonstrated a crucial role in macrophage invasion of parasite and could be an appropriate candidate for leishmaniasis therapy [15]. After promising in vitro trial of the drug by our research team against the Leishmania major promastigotes [18], in the evolution of that study, the in vivo therapeutic effect of cream-based
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