Antileishmanial Activity and Inducible Nitric Oxide Synthase Activation by RuNO Complex.

Abstract:

:Parasites of the genus Leishmania are 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 compound cis-[Ru(bpy)2SO3(NO)]PF6, or RuNO, showed leishmanicidal activity directly and indirectly on promastigote forms of Leishmania (Leishmania) amazonensis. In addition, treatment with RuNO increased NO production by reversing the depletion of NO caused by Leishmania. 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.

journal_name

Mediators Inflamm

authors

Marcusso Orsini T,Kawakami NY,Panis C,Fortes Dos Santos Thomazelli AP,Tomiotto-Pellissier F,Cataneo AH,Kian D,Megumi Yamauchi L,Gouveia Júnior FS,de França Lopes LG,Cecchini R,Nazareth Costa I,Jerley Nogueira da Silva J,Conchon

doi

10.1155/2016/2631625

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

2631625

eissn

0962-9351

issn

1466-1861

journal_volume

2016

pub_type

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