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

Tatiane Marcusso Orsini,Wander Rogério Pavanelli,Fernanda Tomiotto-Pellissier,Florêncio S Gouveia Júnior,Ana Paula Fortes Dos Santos Thomazelli,Danielle Kian,Jean Jerley Nogueira Da Silva,Allan Henrique Depieri Cataneo,Ivete Conchon-Costa,Carolina Panis,Rubens Cecchini,Luiz Gonzaga De França Lopes,Idessânia Nazareth Costa,Lucy Megumi Yamauchi,Natalia Yoshie Kawakami

doi:10.1155/2016/2631625

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.

Highlights

American cutaneous leishmaniasis (ACL) is an endemic disease in Brazil, in which the causative agents are the protozoans Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis
An important one is its ability to interfere with nitric oxide (NO) production, by suppressing the expression of inducible nitric oxide synthase in macrophages, which results in depletion of NO, a key mediator of leishmanicidal activity, able to impair the replication of L. amazonensis [5]
The antileishmanial effect of RuNO complex was evaluated by determining the proliferation of promastigote forms of L. amazonensis

Summary

Introduction

American cutaneous leishmaniasis (ACL) is an endemic disease in Brazil, in which the causative agents are the protozoans Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis. ACL has several clinical forms: localized, disseminated, or diffuse skin lesions and aggressive and mutilating mucocutaneous wounds [1]; manifestations depend on the species of the parasite and the immune response of the host [2]. Leishmania has several mechanisms for escaping the immune response. An important one is its ability to interfere with nitric oxide (NO) production, by suppressing the expression of inducible nitric oxide synthase (iNOS) in macrophages, which results in depletion of NO, a key mediator of leishmanicidal activity, able to impair the replication of L. amazonensis [5]

Methods

Results

Conclusion