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N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin

Human serum albumin (HSA) represents the most abundant plasma protein, with relevant antioxidant activity due to the presence of the sulfhydryl group on cysteine at position 34 (Cys34), the latter being one of the major target sites for redox-dependent modifications leading to the formation of mixed...

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Autores principales: Altomare, Alessandra Anna, Brioschi, Maura, Eligini, Sonia, Bonomi, Alice, Zoanni, Beatrice, Iezzi, Ada, Jemos, Costantino, Porro, Benedetta, D’Alessandra, Yuri, Guarino, Anna, Omodeo Salè, Emanuela, Aldini, Giancarlo, Agostoni, Piergiuseppe, Banfi, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495570/
https://www.ncbi.nlm.nih.gov/pubmed/36139832
http://dx.doi.org/10.3390/antiox11091758
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author Altomare, Alessandra Anna
Brioschi, Maura
Eligini, Sonia
Bonomi, Alice
Zoanni, Beatrice
Iezzi, Ada
Jemos, Costantino
Porro, Benedetta
D’Alessandra, Yuri
Guarino, Anna
Omodeo Salè, Emanuela
Aldini, Giancarlo
Agostoni, Piergiuseppe
Banfi, Cristina
author_facet Altomare, Alessandra Anna
Brioschi, Maura
Eligini, Sonia
Bonomi, Alice
Zoanni, Beatrice
Iezzi, Ada
Jemos, Costantino
Porro, Benedetta
D’Alessandra, Yuri
Guarino, Anna
Omodeo Salè, Emanuela
Aldini, Giancarlo
Agostoni, Piergiuseppe
Banfi, Cristina
author_sort Altomare, Alessandra Anna
collection PubMed
description Human serum albumin (HSA) represents the most abundant plasma protein, with relevant antioxidant activity due to the presence of the sulfhydryl group on cysteine at position 34 (Cys34), the latter being one of the major target sites for redox-dependent modifications leading to the formation of mixed disulfide linkages with low molecular weight thiols. Thiolated forms of HSA (Thio-HSA) may be useful as markers of an unbalanced redox state and as a potential therapeutic target. Indeed, we have previously reported that albumin Cys34 can be regenerated in vitro by N-Acetylcysteine (NAC) through a thiol-disulfide breaking mechanism, with a full recovery of the HSA antioxidant and antiplatelet activities. With this case study, we aimed to assess the ability of NAC to regenerate native mercaptoalbumin (HSA-SH) and the plasma antioxidant capacity in subjects with redox unbalance, after oral and intravenous administration. A placebo-controlled crossover study, single-blinded, was performed on six hypertensive subjects, randomized into two groups, on a one-to-one basis with NAC (600 mg/die) or a placebo, orally and intravenously administered. Albumin isoforms, HSA-SH, Thio-HSA, and glutathione levels were evaluated by means of mass spectrometry. The plasma antioxidant activity was assessed by a fluorimetric assay. NAC, orally administered, significantly decreased the Thio-HSA levels in comparison with the pre-treatment conditions (T0), reaching the maximal effect after 60 min (−24.7 ± 8%). The Thio-HSA reduction was accompanied by a concomitant increase in the native HSA-SH levels (+6.4 ± 2%). After intravenous administration of NAC, a significant decrease of the Thio-HSA with respect to the pre-treatment conditions (T0) was observed, with a maximal effect after 30 min (−68.9 ± 10.6%) and remaining significant even after 6 h. Conversely, no effect on the albumin isoforms was detected with either the orally or the intravenously administered placebo treatments. Furthermore, the total antioxidant activity of the plasma significantly increased after NAC infusion with respect to the placebo (p = 0.0089). Interestingly, we did not observe any difference in terms of total glutathione corrected for hemoglobin, ruling out any effect of NAC on the intracellular glutathione and supporting its role as a disulfide-breaking agent. This case study confirms the in vitro experiments and demonstrates for the first time that NAC is able to regenerate mercaptoalbumin in vivo, allowing us to hypothesize that the recovery of Cys34 content can modulate in vivo oxidative stress and, hopefully, have an effect in oxidative-based diseases.
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spelling pubmed-94955702022-09-23 N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin Altomare, Alessandra Anna Brioschi, Maura Eligini, Sonia Bonomi, Alice Zoanni, Beatrice Iezzi, Ada Jemos, Costantino Porro, Benedetta D’Alessandra, Yuri Guarino, Anna Omodeo Salè, Emanuela Aldini, Giancarlo Agostoni, Piergiuseppe Banfi, Cristina Antioxidants (Basel) Article Human serum albumin (HSA) represents the most abundant plasma protein, with relevant antioxidant activity due to the presence of the sulfhydryl group on cysteine at position 34 (Cys34), the latter being one of the major target sites for redox-dependent modifications leading to the formation of mixed disulfide linkages with low molecular weight thiols. Thiolated forms of HSA (Thio-HSA) may be useful as markers of an unbalanced redox state and as a potential therapeutic target. Indeed, we have previously reported that albumin Cys34 can be regenerated in vitro by N-Acetylcysteine (NAC) through a thiol-disulfide breaking mechanism, with a full recovery of the HSA antioxidant and antiplatelet activities. With this case study, we aimed to assess the ability of NAC to regenerate native mercaptoalbumin (HSA-SH) and the plasma antioxidant capacity in subjects with redox unbalance, after oral and intravenous administration. A placebo-controlled crossover study, single-blinded, was performed on six hypertensive subjects, randomized into two groups, on a one-to-one basis with NAC (600 mg/die) or a placebo, orally and intravenously administered. Albumin isoforms, HSA-SH, Thio-HSA, and glutathione levels were evaluated by means of mass spectrometry. The plasma antioxidant activity was assessed by a fluorimetric assay. NAC, orally administered, significantly decreased the Thio-HSA levels in comparison with the pre-treatment conditions (T0), reaching the maximal effect after 60 min (−24.7 ± 8%). The Thio-HSA reduction was accompanied by a concomitant increase in the native HSA-SH levels (+6.4 ± 2%). After intravenous administration of NAC, a significant decrease of the Thio-HSA with respect to the pre-treatment conditions (T0) was observed, with a maximal effect after 30 min (−68.9 ± 10.6%) and remaining significant even after 6 h. Conversely, no effect on the albumin isoforms was detected with either the orally or the intravenously administered placebo treatments. Furthermore, the total antioxidant activity of the plasma significantly increased after NAC infusion with respect to the placebo (p = 0.0089). Interestingly, we did not observe any difference in terms of total glutathione corrected for hemoglobin, ruling out any effect of NAC on the intracellular glutathione and supporting its role as a disulfide-breaking agent. This case study confirms the in vitro experiments and demonstrates for the first time that NAC is able to regenerate mercaptoalbumin in vivo, allowing us to hypothesize that the recovery of Cys34 content can modulate in vivo oxidative stress and, hopefully, have an effect in oxidative-based diseases. MDPI 2022-09-06 /pmc/articles/PMC9495570/ /pubmed/36139832 http://dx.doi.org/10.3390/antiox11091758 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Altomare, Alessandra Anna
Brioschi, Maura
Eligini, Sonia
Bonomi, Alice
Zoanni, Beatrice
Iezzi, Ada
Jemos, Costantino
Porro, Benedetta
D’Alessandra, Yuri
Guarino, Anna
Omodeo Salè, Emanuela
Aldini, Giancarlo
Agostoni, Piergiuseppe
Banfi, Cristina
N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title_full N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title_fullStr N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title_full_unstemmed N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title_short N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin
title_sort n-acetylcysteine regenerates in vivo mercaptoalbumin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495570/
https://www.ncbi.nlm.nih.gov/pubmed/36139832
http://dx.doi.org/10.3390/antiox11091758
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