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Type: Artigo de periódico
Title: S-nitrosoglutathione (gsno) Is Cytotoxic To Intracellular Amastigotes And Promotes Healing Of Topically Treated Leishmania Major Or Leishmania Braziliensis Skin Lesions
Author: Costa I.S.F.
de Souza G.F.P.
de Oliveira M.G.
Abrahamsohn I.D.A.
Abstract: This study wasdesigned to verify the cytotoxic activity of S-nitrosoglutathione (GSNO) against intracellular Leishmania amastigotes and to test its efficacy as a topical treatment of localized cutaneous leishmaniasis (LCL) in Leishmania major- or Leishmania braziliensis-infected mice.Cytotoxic activity of GSNO was verified in L. major-infected THP-1 macrophages. S-nitrosated proteins were detected by immunofluorescence. Topical treatment was done by daily application of a solution of GSNO in PBS to the skin ulcer of Leishmania-infected mice. BALB/c and interferon-γ-knockout (IFN-γ-KO) C57BL/6 mice were infected with L. major and L. braziliensis, respectively. Ulcer size was measured weekly and the parasite loads were determined in the lesion and lymph nodes. Controls received PBS topically or amphotericin B (AMB) intravenously.The number of intracellular L. major amastigotes was markedly reduced in GSNO-treated cultures; in these, staining for S-nitrosated proteins was present in the cytoplasm and colocalized with intracellular amastigotes. Topical treatment with GSNO of L. major ulcers in BALB/c mice suppressed lesion growth, reduced the parasite loadandinduced healingcomparable to the effectof intravenouslyadministeredAMB.TopicalGSNOtreatment was also efficient at suppressing lesion growth in IFN-γ-KO mice infected with L. braziliensis.GSNO is cytotoxic to intracellular L. majoramastigotes in vitro and had a healing effect on LCL caused by L. majorandL. braziliensis in mice. These positive results onthe topical therapeutic effectofGSNOinmouseleishmaniasis infections provide the experimental basis for a possible future trial in the treatment of human LCL. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Rights: fechado
Identifier DOI: 10.1093/jac/dkt210
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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