Antileishmanial Activity and Inducible Nitric Oxide Synthase Activation by RuNO Complex.
Tatiane Marcusso OrsiniNatalia Yoshie KawakamiCarolina PanisAna Paula Fortes Dos Santos ThomazelliFernanda Tomiotto-PellissierAllan Henrique Depieri CataneoDanielle KianLucy Megumi YamauchiFlorêncio S Gouveia JúniorLuiz Gonzaga de França LopesRubens CecchiniIdessânia Nazareth CostaJean Jerley Nogueira da SilvaIvete Conchon CostaWander Rogério PavanelliPublished in: Mediators of inflammation (2016)
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.
Keyphrases
- nitric oxide synthase
- nitric oxide
- signaling pathway
- poor prognosis
- lps induced
- oxidative stress
- gene expression
- cell proliferation
- single cell
- risk assessment
- pi k akt
- binding protein
- hydrogen peroxide
- long non coding rna
- nuclear factor
- immune response
- inflammatory response
- bone marrow
- toll like receptor
- trypanosoma cruzi