Donor compounds GSNO and SNAC action of nitric oxide on Leishmania major in macrophage cultures and infected mice

• Grant number: 07/01776-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2007
• End date: July 31, 2009
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ises de Almeida Abrahamsohn
• Grantee: Inez Silva Fernandes de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The protozoa of the genus Leishmania are the etiological agents of visceral and cutaneous leishmaniasis. The intracellular macrophage infection by these microorganisms is controlled by oxygen and nitrogen intermediate radicals generated by the host cell. Molecules generically known as nitric oxide (NO) donors are toxic to Leishmania promastigotes and have been tested as topic therapy of human Leishmania ulcers. Recently, the compounds S-nitrosoglutathione (GSNO) and S- nitroso-N-acetyl-L-cysteine (SNAC) were tested in promastigote cultures of Leishmania amazonensis and killed the parasites. These molecules are more stable and are presently being tested in clinical trials for their potential healing effects on ischemic ulcers. On the other hand, often the healing effect of the classic systemic antimonial treatment on leishmaniasis ulcers is slow and in consequence is frequently abandoned by the patient. Therefore, new compounds or therapies that eliminate the parasite and/or accelerate the cure are being investigated. The present project aims to investigate the toxic activity of GSNO and SNAC on intracellular Leishmania major amastigotes in a human macrophage cell line in culture. In addition, the effect of topical application of gel-incorporated-GSNO on the healing of ulcerated dorsal skin Leishmania ulcers will be tested in BALB/c mice: the lesion development and local parasite load will be evaluated. Subsequently the mechanisms of toxicity will be investigated and the investigation will be extended to other Leishmania species.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES COSTA, INEZ SILVA; PEREIRA DE SOUZA, GABRIELA FREITAS; DE OLIVEIRA, MARCELO GANZAROLLI; ABRAHAMSOHN, ISES DE ALMEIDA. S-nitrosoglutathione (GSNO) is cytotoxic to intracellular amastigotes and promotes healing of topically treated Leishmania major or Leishmania braziliensis skin lesions. Journal of Antimicrobial Chemotherapy, v. 68, n. 11, p. 2561-2568, NOV 2013. (07/01776-1)