S-nitrosoglutathione (GSNO) is cytotoxic to intracellular amastigotes and promotes healing of topically treated Leishmania major or Leishmania braziliensis skin lesions

Author(s)

Fernandes Costa, Inez Silva ^[1] ; Pereira de Souza, Gabriela Freitas ^[2] ; de Oliveira, Marcelo Ganzarolli ^[2] ; Abrahamsohn, Ises de Almeida ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Inst Quim, Dept Quim Fis, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Antimicrobial Chemotherapy; v. 68, n. 11, p. 2561-2568, NOV 2013.
• Web of Science Citations: 13

Abstract

Objectives: This study was designed 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 ({[}CL) in Leishmania major- or Leishmania braziliensis-infected mice. Methods: 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-gamma-knockout (IFN-gamma-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. Results: 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 load and induced healing comparable to the effect of intravenously administered AMB. Topical GSNO treatment was also efficient at suppressing lesion growth in IFN-gamma-KO mice infected with L. braziliensis. Conclusions: GSNO is cytotoxic to intracellular L. major amastigotes in vitro and had a healing effect on LCL caused by L. major and L. braziliensis in mice. These positive results on the topical therapeutic effect of GSNO in mouse leishmaniasis infections provide the experimental basis for a possible future trial in the treatment of human LCL. (AU)

• FAPESP's process: 07/01776-1 - Donor compounds GSNO and SNAC action of nitric oxide on Leishmania major in macrophage cultures and infected mice
• Grantee: Inez Silva Fernandes de Souza
• Support Opportunities: Scholarships in Brazil - Master