Sodium nitroprusside has leishmanicidal activity independent of iNOS

Abstract

Introduction: Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania. Cutaneous leishmaniasis is the most common form, with millions of new cases worldwide each year. Treatments are ineffective due to the toxicity of existing drugs and the resistance acquired by certain strains of the parasite. Methods: We evaluated the activity of sodium nitroprusside in macrophages infected with Leishmania (Leishmania) amazonensis. Phagocytic and microbicidal activity were evaluated by phagocytosis assay and promastigote recovery, respectively, while cytokine production and nitrite levels were determined by ELISA and by the Griess method. Levels of iNOS and 3-nitrotyrosine were measured by immunocytochemistry. Results: Sodium nitroprusside exhibited in vitro antileishmanial activity at both concentrations tested, reducing the number of amastigotes and recovered promastigotes in macrophages infected with L. amazonensis. At 1.5μg/mL, sodium nitroprusside stimulated levels of TNF-α and nitric oxide, but not IFN-γ. The compound also increased levels of 3-nitrotyrosine, but not expression of iNOS, suggesting that the drug acts as an exogenous source of nitric oxide. Conclusions: Sodium nitroprusside enhances microbicidal activity in Leishmania-infected macrophages by boosting nitric oxide and 3-nitrotyrosine.