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Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial

Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been sho...

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Autores principales: Safe, Izabella P., Amaral, Eduardo P., Araújo-Pereira, Mariana, Lacerda, Marcus V. G., Printes, Vitoria S., Souza, Alexandra B., Beraldi-Magalhães, Francisco, Monteiro, Wuelton M., Sampaio, Vanderson S., Barreto-Duarte, Beatriz, Andrade, Alice M. S., Spener-Gomes, Renata, Costa, Allyson Guimarães, Cordeiro-Santos, Marcelo, Andrade, Bruno B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889506/
https://www.ncbi.nlm.nih.gov/pubmed/33613521
http://dx.doi.org/10.3389/fimmu.2020.602589
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author Safe, Izabella P.
Amaral, Eduardo P.
Araújo-Pereira, Mariana
Lacerda, Marcus V. G.
Printes, Vitoria S.
Souza, Alexandra B.
Beraldi-Magalhães, Francisco
Monteiro, Wuelton M.
Sampaio, Vanderson S.
Barreto-Duarte, Beatriz
Andrade, Alice M. S.
Spener-Gomes, Renata
Costa, Allyson Guimarães
Cordeiro-Santos, Marcelo
Andrade, Bruno B.
author_facet Safe, Izabella P.
Amaral, Eduardo P.
Araújo-Pereira, Mariana
Lacerda, Marcus V. G.
Printes, Vitoria S.
Souza, Alexandra B.
Beraldi-Magalhães, Francisco
Monteiro, Wuelton M.
Sampaio, Vanderson S.
Barreto-Duarte, Beatriz
Andrade, Alice M. S.
Spener-Gomes, Renata
Costa, Allyson Guimarães
Cordeiro-Santos, Marcelo
Andrade, Bruno B.
author_sort Safe, Izabella P.
collection PubMed
description Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.
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spelling pubmed-78895062021-02-19 Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial Safe, Izabella P. Amaral, Eduardo P. Araújo-Pereira, Mariana Lacerda, Marcus V. G. Printes, Vitoria S. Souza, Alexandra B. Beraldi-Magalhães, Francisco Monteiro, Wuelton M. Sampaio, Vanderson S. Barreto-Duarte, Beatriz Andrade, Alice M. S. Spener-Gomes, Renata Costa, Allyson Guimarães Cordeiro-Santos, Marcelo Andrade, Bruno B. Front Immunol Immunology Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7889506/ /pubmed/33613521 http://dx.doi.org/10.3389/fimmu.2020.602589 Text en Copyright © 2021 Safe, Amaral, Araújo-Pereira, Lacerda, Printes, Souza, Beraldi-Magalhães, Monteiro, Sampaio, Barreto-Duarte, Andrade, Spener-Gomes, Costa, Cordeiro-Santos and Andrade http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Safe, Izabella P.
Amaral, Eduardo P.
Araújo-Pereira, Mariana
Lacerda, Marcus V. G.
Printes, Vitoria S.
Souza, Alexandra B.
Beraldi-Magalhães, Francisco
Monteiro, Wuelton M.
Sampaio, Vanderson S.
Barreto-Duarte, Beatriz
Andrade, Alice M. S.
Spener-Gomes, Renata
Costa, Allyson Guimarães
Cordeiro-Santos, Marcelo
Andrade, Bruno B.
Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title_full Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title_fullStr Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title_full_unstemmed Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title_short Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial
title_sort adjunct n-acetylcysteine treatment in hospitalized patients with hiv-associated tuberculosis dampens the oxidative stress in peripheral blood: results from the ripenactb study trial
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889506/
https://www.ncbi.nlm.nih.gov/pubmed/33613521
http://dx.doi.org/10.3389/fimmu.2020.602589
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