title: Antileishmanial Activity and Inducible Nitric Oxide Synthase Activation by RuNO Complex.
abstract: Parasites of the genusLeishmaniaare capable of inhibiting effector functions of macrophages. These parasites have developed the adaptive ability to escape host defenses; for example, they inactivate the NF-κB complex and suppress iNOS expression in infected macrophages, which are responsible for the production of the major antileishmanial substance nitric oxide (NO), favoring then its replication and successful infection. Metal complexes with NO have been studied as potential compounds for the treatment of certain tropical diseases, such as ruthenium compounds, known to be exogenous NO donors. In the present work, the compoundcis-[Ru(bpy)2SO3(NO)]PF6, or RuNO, showed leishmanicidal activity directly and indirectly on promastigote forms ofLeishmania (Leishmania) amazonensis. In addition, treatment with RuNO increased NO production by reversing the depletion of NO caused byLeishmania. We also found increased expression of Akt, iNOS, and NF-κB in infected and treated macrophages. These results demonstrated that RuNO was able to kill the parasite by NO release and modulate the transcriptional capacity of the cell.
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Tatiane
authors: 0000-0003-4070-9201
authors: T
authors: Marcusso Orsini
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Natalia Yoshie
authors: NY
authors: Kawakami
authors: Laboratory of Inflammatory Mediators, State University of Western Paraná, 85605-010 Francisco Beltrão, PR, Brazil.
authors: Carolina
authors: 0000-0002-0104-4369
authors: C
authors: Panis
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Ana Paula
authors: AP
authors: Fortes Dos Santos Thomazelli
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Fernanda
authors: F
authors: Tomiotto-Pellissier
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Allan Henrique Depieri
authors: 0000-0002-3567-7471
authors: AH
authors: Cataneo
authors: Department of Microbiology, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Danielle
authors: D
authors: Kian
authors: Department of Microbiology, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Lucy
authors: L
authors: Megumi Yamauchi
authors: Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60020-181 Fortaleza, CE, Brazil.
authors: Florêncio S
authors: FS
authors: Gouveia Júnior
authors: Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60020-181 Fortaleza, CE, Brazil.
authors: Luiz Gonzaga
authors: LG
authors: de França Lopes
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Rubens
authors: R
authors: Cecchini
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Idessânia
authors: I
authors: Nazareth Costa
authors: Department of Chemistry, State University of Roraima, 69310-000 Boa Vista, RR, Brazil.
authors: Jean
authors: J
authors: Jerley Nogueira da Silva
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Ivete
authors: 0000-0002-9800-2068
authors: I
authors: Conchon-Costa
authors: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors: Wander Rogério
authors: 0000-0003-1734-7038
authors: WR
authors: Pavanelli
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017975:Ruthenium Compounds / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D016328:NF-kappa B; D009603:Nitroso Compounds; D017975:Ruthenium Compounds; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt