title: Sodium nitroprusside has leishmanicidal activity independent of iNOS.
abstract: BACKGROUND
  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.
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Natália Yoshie
authors.initials: NY
authors.lastname: Kawakami
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tomiotto-Pellissier
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Allan Henrique Depieri
authors.initials: AH
authors.lastname: Cataneo
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Tatiane Marcusso
authors.initials: TM
authors.lastname: Orsini
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Ana Paula Fortes Dos Santos
authors.initials: AP
authors.lastname: Thomazelli
authors.affiliation: Laboratório de Mediadores Inflamatórios, Universidade Estadual do Oeste do Paraná, Francisco Beltrão, Paraná, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Panis
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Ivete
authors.initials: I
authors.lastname: Conchon-Costa
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Wander Rogério
authors.initials: WR
authors.lastname: Pavanelli
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D017737:Macrophages, Peritoneal / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D014344:Trypanocidal Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine