Immunomodulatory role of ATP inhibitor: glibenclamide and its impact on the pathogenesis of murine Leishmania major infection

Abstract

Background Leishmania major is the causative agent of cutaneous leishmaniasis in humans. It can also induce visceral or viscerotropic systemic leishmaniasis in humans. Resistance to treatment has been reported in many countries. Glibenclamide (GB) has been found to enhance treatment in resistant cases. Aim The aim of this work was to study the immunomodulatory effect of ATP inhibitor-GB on leishmaniasis caused by L. major . Materials and methods Mice were divided into three groups: group I (GI), noninfected group; group II (GII), infected with L. major ; and group III (GIII), infected with L. major and treated with GB, starting 10 days postinfection till the end of the experiment. Evaluation was performed by measuring the size of cutaneous skin lesions, histopathological examination of the liver and spleen, and detection of expression of interferon γ, tumor necrosis factor α, interleukin (IL)-4, and IL-10 cytokines by reverse transcriptase real-time PCR. Transmission electron microscopic study of parasites from peritoneal exudate of GII and GIII mice was also carried out. Results The treated group showed a reduction in skin lesion size, improvement in histopathological manifestations, increased expression of interferon γ, and decreased tumor necrosis factor α, IL-4, and IL-10 expression. Transmission electron microscopic study showed vacuolation and damage of parasites in the treated group. Conclusion GB can be used effectively for the treatment of leishmaniasis.