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Type: Artigo de periódico
Title: Leishmanicidal Activity Of Primary S-nitrosothiols Against Leishmania Major And Leishmania Amazonensis: Implications For The Treatment Of Cutaneous Leishmaniasis.
Author: de Souza, Gabriela Freitas Pereira
Yokoyama-Yasunaka, Jenicer K U
Seabra, Amedea Barozzi
Miguel, Danilo Ciccone
de Oliveira, Marcelo Ganzarolli
Uliana, Silvia Reni B
Abstract: Nitric oxide (NO) is considered a key molecule in the defense against intracellular pathogens, particularly Leishmania. The expression of inducible nitric oxide synthase and consequent production of NO by infected macrophages has been shown to correlate with leishmaniasis resistance in the murine model as well as in human patients. Nitric oxide donors have been used successfully in the treatment of cutaneous leishmaniasis in humans, although their mechanisms of action are not fully understood. In the present work, the dose-dependent cytotoxic effects of the NO-donors S-nitroso-N-acetyl-l-cysteine (SNAC) and S-nitrosoglutathione (GSNO) against Leishmania were evaluated. GSNO inhibited the growth of Leishmania major and Leishmania amazonensis with in vitro 50% inhibitory concentrations (IC(50)) of 68.8+/-22.86 and 68.9+/-7.9 micromol L(-1), respectively. The IC(50) for SNAC against L. major and L. amazonensis were, respectively, 54.6+/-8.3 and 181.6+/-12.5 micromol L(-1). The leishmanicidal activity of GSNO, but not of SNAC, was reversed by ascorbic acid (AA) and dithiothreitol (DTT), suggesting that the mechanism of action of GSNO is related to the transnitrosation of parasite proteins. These results demonstrate that SNAC and GSNO have leishmanicidal activity, and are thus potential therapeutic agents against cutaneous leishmaniasis.
Subject: Acetylcysteine
Cell Survival
Leishmania Major
Leishmaniasis, Cutaneous
Nitric Oxide
Nitric Oxide Donors
Citation: Nitric Oxide : Biology And Chemistry / Official Journal Of The Nitric Oxide Society. v. 15, n. 3, p. 209-16, 2006-Nov.
Rights: fechado
Identifier DOI: 10.1016/j.niox.2006.01.011
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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