Research Article Antileishmanial Activity and Inducible Nitric Oxide Synthase Activation by RuNO Complex Tatiane Marcusso Orsini, 1 Natalia Yoshie Kawakami, 1 Carolina Panis, 2 Ana Paula Fortes dos Santos Thomazelli, 1 Fernanda Tomiotto-Pellissier, 1 Allan Henrique Depieri Cataneo, 1 Danielle Kian, 3 Lucy Megumi Yamauchi, 3 Florêncio S. Gouveia Júnior, 4 Luiz Gonzaga de França Lopes, 4 Rubens Cecchini, 1 Idessânia Nazareth Costa, 1 Jean Jerley Nogueira da Silva, 5 Ivete Conchon-Costa, 1 and Wander Rogério Pavanelli 1 1 Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil 2 Laboratory of Infammatory Mediators, State University of Western Paran´ a, 85605-010 Francisco Beltr˜ ao, PR, Brazil 3 Department of Microbiology, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil 4 Department of Organic and Inorganic Chemistry, Federal University of Cear´ a, 60020-181 Fortaleza, CE, Brazil 5 Department of Chemistry, State University of Roraima, 69310-000 Boa Vista, RR, Brazil Correspondence should be addressed to Wander Rog´ erio Pavanelli; wanderpavanelli@yahoo.com.br Received 23 February 2016; Revised 4 July 2016; Accepted 17 July 2016 Academic Editor: Chiara De Luca Copyright © 2016 Tatiane Marcusso Orsini et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Parasites of the genus Leishmania are capable of inhibiting efector functions of macrophages. Tese parasites have developed the adaptive ability to escape host defenses; for example, they inactivate the NF-B 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) 2 SO 3 (NO)]PF 6 , 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-B in infected and treated macrophages. Tese results demonstrated that RuNO was able to kill the parasite by NO release and modulate the transcriptional capacity of the cell. 1. 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 difuse skin lesions and aggressive and mutilating mucocutaneous wounds [1]; manifestations depend on not only the species of the parasite but also the immune response of the host [2]. Te recommended treatment of ACL is the use of pen- tavalent antimonials such as sodium stibogluconate (Pen- tostam5) and methylglucamine antimoniate (Glucantime5) [3]. However, the treatment has several side efects, such as nausea, vomiting, and hepatic and cardiotoxicity, leading patients to discontinue treatment and favoring the emergence of resistant strains [4]. Leishmania has several mechanisms for escaping the immune response. An important one is its ability to inter- fere with nitric oxide (NO) production, by suppressing the expression of inducible nitric oxide synthase (iNOS) in macrophages, which consequently results in depletion of NO, a key mediator of leishmanicidal activity, able to impair the replication of L. amazonensis [5]. Te activation of iNOS is dependent on NF-B tran- scription. Parasites of the genus Leishmania can cleave the Hindawi Publishing Corporation Mediators of Inflammation Volume 2016, Article ID 2631625, 10 pages http://dx.doi.org/10.1155/2016/2631625