Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/18069
Title: N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions
Authors: Amaral, Eduardo P
Conceição, Elisabete Lopes
Costa, Diego Luis
Rocha, Michael Santos
Marinho, Jamocyr Moura
Santos, Marcelo Cordeiro
Lima, Maria Regina D'Império
Barbosa, Theolis Costa
Sher, Alan
Andrade, Bruno de Bezerril
Affilliation: National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA / Infectious Diseases, University of São Paulo. Institute of Biomedical Science. Department of Immunology. Laboratory of Immunology. São Paulo, SP, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde (ICS). Salvador, BA, Brasil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Salvador, BA, Brasil
School of Medicine and Public Health. Departament of Internal Medicine. Salvador, BA, Brasil / Hospital Especializado Octávio Mangabeira. Salvador, BA, Brasil
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Departamento de Ensino e Pós-Graduação. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-Graduação em Medicina Tropical. Manaus, AM, Brasil
Infectious Diseases, University of São Paulo. Institute of Biomedical Science. Department of Immunology. Laboratory of Immunology. São Paulo, SP, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde (ICS). Salvador, BA, Brasil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, MD, USA / Infectious Diseases, University of São Paulo. Institute of Biomedical Science. Department of Immunology. Laboratory of Immunology. São Paulo, SP, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunorregulação (LIMI). Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil
Abstract: Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Methods: Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. Results: PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. Conclusions: NAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.
Keywords: Tuberculosis
N-acetyl cysteine
Antimicrobial activity
Therapy
keywords: Tuberculose
N-acetil cisteína
Actividade antimicrobiana
Terapia
Issue Date: 2016
Publisher: BioMed Central
Citation: AMARAL, E. P. et al. N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions. BMC Microbiology, v. 16, p. 251, 2016.
DOI: 10.1186/s12866-016-0872-7
ISSN: 1471-2180
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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