Biomedicine & Pharmacotherapy (Apr 2022)
Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19
- Jordana Grazziela A. Coelho dos Reis,
- Geovane Marques Ferreira,
- Alice Aparecida Lourenço,
- Ágata Lopes Ribeiro,
- Camila Pacheco da Silveira Martins da Mata,
- Patrícia de Melo Oliveira,
- Daisymara Priscila de Almeida Marques,
- Linziane Lopes Ferreira,
- Felipe Alves Clarindo,
- Murillo Ferreira da Silva,
- Heitor Portella Póvoas Filho,
- Nilson Roberto Ribeiro Oliveira, Jr,
- Maisah Meyhr D’Carmo Sodré,
- Sandra Rocha Gadelha,
- George Rego Albuquerque,
- Bianca Mendes Maciel,
- Ana Paula Melo Mariano,
- Mylene de Melo Silva,
- Renato Fontana,
- Lauro Juliano Marin,
- Renata Santiago Alberto Carlos,
- Amanda Teixeira Sampaio Lopes,
- Fabrício Barbosa Ferreira,
- Uener Ribeiro dos Santos,
- Íris Terezinha Santos de Santana,
- Hllytchaikra Ferraz Fehlberg,
- Rachel Passos Rezende,
- João Carlos T. Dias,
- Eduardo Gross,
- Gisele Assis Castro Goulart,
- Marie Gabriele Santiago,
- Ana Paula Motta Lavigne de Lemos,
- Aline O. da Conceição,
- Carla Cristina Romano,
- Luciana Debortoli de Carvalho,
- Olindo Assis Martins Filho,
- Claudio Almeida Quadros,
- David L. Morris,
- Sarah J. Valle
Affiliations
- Jordana Grazziela A. Coelho dos Reis
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; Correspondence to: Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627 Campus Pampulha, Belo Horizonte CEP: 31270-901, MG, Brazil.
- Geovane Marques Ferreira
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Alice Aparecida Lourenço
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Ágata Lopes Ribeiro
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Camila Pacheco da Silveira Martins da Mata
- Risoleta Tolentino Neves Hospital, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Patrícia de Melo Oliveira
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Daisymara Priscila de Almeida Marques
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Linziane Lopes Ferreira
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Felipe Alves Clarindo
- Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Murillo Ferreira da Silva
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil; Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Heitor Portella Póvoas Filho
- Hospital de Ilhéus, Ilhéus, BA, Brazil
- Nilson Roberto Ribeiro Oliveira, Jr
- Hospital de Ilhéus, Ilhéus, BA, Brazil
- Maisah Meyhr D’Carmo Sodré
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Sandra Rocha Gadelha
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil; Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- George Rego Albuquerque
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil; Department of Agricultural and Environmental Sciences (DCAA), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Bianca Mendes Maciel
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil; Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Ana Paula Melo Mariano
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil; Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Mylene de Melo Silva
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Renato Fontana
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil; Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Lauro Juliano Marin
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil; Department of Health Sciences (DCS), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Renata Santiago Alberto Carlos
- Department of Agricultural and Environmental Sciences (DCAA), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Amanda Teixeira Sampaio Lopes
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Fabrício Barbosa Ferreira
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Uener Ribeiro dos Santos
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- Íris Terezinha Santos de Santana
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Hllytchaikra Ferraz Fehlberg
- Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil
- Rachel Passos Rezende
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- João Carlos T. Dias
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- Eduardo Gross
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- Gisele Assis Castro Goulart
- Department of Pharmaceuticals, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Marie Gabriele Santiago
- Department of Pharmaceuticals, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Ana Paula Motta Lavigne de Lemos
- Hospital de Ilhéus, Ilhéus, BA, Brazil
- Aline O. da Conceição
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- Carla Cristina Romano
- Hospital de Ilhéus, Ilhéus, BA, Brazil
- Luciana Debortoli de Carvalho
- Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil
- Olindo Assis Martins Filho
- Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, MG, Brazil
- Claudio Almeida Quadros
- São Rafael Hospital and Bahia State University, Salvador, Bahia, Brazil
- David L. Morris
- Mucpharm Pty Ltd, Sydney, NSW, Australia; University of New South Wales, St George & Sutherland Hospital Clinical School, Sydney, NSW, Australia; Department of Surgery, St George Hospital, Sydney, NSW, Australia; Corresponding author at: University of New South Wales, St George & Sutherland Hospital Clinical School, Sydney, NSW, Australia.
- Sarah J. Valle
- Mucpharm Pty Ltd, Sydney, NSW, Australia; University of New South Wales, St George & Sutherland Hospital Clinical School, Sydney, NSW, Australia; Corresponding author at: Mucpharm Pty Ltd, Sydney NSW 2217 Australia.
- Journal volume & issue
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Vol. 148
p. 112753
Abstract
COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Method: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. Results: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. Conclusion: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.