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Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19 - 16/03/22

Doi : 10.1016/j.biopha.2022.112753 
Jordana Grazziela A. Coelho dos Reis a, , Geovane Marques Ferreira a, Alice Aparecida Lourenço a, Ágata Lopes Ribeiro a, Camila Pacheco da Silveira Martins da Mata b, Patrícia de Melo Oliveira a, Daisymara Priscila de Almeida Marques a, Linziane Lopes Ferreira a, Felipe Alves Clarindo a, Murillo Ferreira da Silva c, d, Heitor Portella Póvoas Filho e, Nilson Roberto Ribeiro Oliveira e, Maisah Meyhr D’Carmo Sodré d, Sandra Rocha Gadelha c, d, George Rego Albuquerque d, f, Bianca Mendes Maciel c, d, Ana Paula Melo Mariano c, d, Mylene de Melo Silva d, Renato Fontana c, d, Lauro Juliano Marin d, g, Renata Santiago Alberto Carlos f, Amanda Teixeira Sampaio Lopes d, Fabrício Barbosa Ferreira d, Uener Ribeiro dos Santos c, Íris Terezinha Santos de Santana d, Hllytchaikra Ferraz Fehlberg d, Rachel Passos Rezende c, João Carlos T. Dias c, Eduardo Gross c, Gisele Assis Castro Goulart h, Marie Gabriele Santiago h, Ana Paula Motta Lavigne de Lemos e, Aline O. da Conceição c, Carla Cristina Romano e, Luciana Debortoli de Carvalho c, Olindo Assis Martins Filho i, Claudio Almeida Quadros j, David L. Morris k, l, m, , Sarah J. Valle k, l,
a Basic and Applied Virology Laboratory, Department of Microbiology, Institute for Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil 
b Risoleta Tolentino Neves Hospital, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil 
c Department of Biological Sciences, Santa Cruz State University, Ilhéus, BA, Brazil 
d Laboratory of Pharmacogenomics and Molecular Epidemiology (LAFEM), Santa Cruz State University (UESC), Ilhéus, BA, Brazil 
e Hospital de Ilhéus, Ilhéus, BA, Brazil 
f Department of Agricultural and Environmental Sciences (DCAA), Santa Cruz State University (UESC), Ilhéus, BA, Brazil 
g Department of Health Sciences (DCS), Santa Cruz State University (UESC), Ilhéus, BA, Brazil 
h Department of Pharmaceuticals, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil 
i Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, MG, Brazil 
j São Rafael Hospital and Bahia State University, Salvador, Bahia, Brazil 
k Mucpharm Pty Ltd, Sydney, NSW, Australia 
l University of New South Wales, St George & Sutherland Hospital Clinical School, Sydney, NSW, Australia 
m Department of Surgery, St George Hospital, Sydney, NSW, Australia 

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.Department of Microbiology, Instituto de Ciências Biológicas, Universidade Federal de Minas GeraisAv. Antônio Carlos 6627 Campus PampulhaBelo HorizonteMGCEP: 31270-901Brazil⁎⁎Corresponding author at: University of New South Wales, St George & Sutherland Hospital Clinical School, Sydney, NSW, Australia.University of New South Wales, St George & Sutherland Hospital Clinical SchoolSydneyNSWAustralia⁎⁎⁎Corresponding author at: Mucpharm Pty Ltd, Sydney NSW 2217 Australia.Mucpharm Pty LtdSydneyNSW2217Australia

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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.

El texto completo de este artículo está disponible en PDF.

Highlights

BromAc is a strong mucolytic for COVID-19 sputum ex vivo.
Select chemokines and cytokines were downregulated following BromAc exposure.
Mucolytic and anti-inflammatory effects of BromAc were dose-dependent.
Further assessment of BromAc in COVID-19 clinical trials is warranted.

El texto completo de este artículo está disponible en PDF.

Keywords : BromAc, COVID-19, Tracheal aspirate, SARS-CoV-2, Mucolytic therapy


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© 2022  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 148

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