Glutathione deficiency and heart failure: a systematic review of human and animal evidence

Background: Oxidative stress is an important factor underlying several pathophysiological mechanisms in heart failure (HF). Nevertheless, modulating oxidative stress is still a significant challenge due to the lack of specific and modifiable targets. A central component that is integrated into sever...

Full description

Saved in:
Bibliographic Details
Main Authors: Ali A. Al-Mubarak, Antonio Esquivel-Gaytan, Herman H.W. Silljé, Peter van der Meer, Nils Bomer
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Advances in Redox Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667137925000128
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849732684419432448
author Ali A. Al-Mubarak
Antonio Esquivel-Gaytan
Herman H.W. Silljé
Peter van der Meer
Nils Bomer
author_facet Ali A. Al-Mubarak
Antonio Esquivel-Gaytan
Herman H.W. Silljé
Peter van der Meer
Nils Bomer
author_sort Ali A. Al-Mubarak
collection DOAJ
description Background: Oxidative stress is an important factor underlying several pathophysiological mechanisms in heart failure (HF). Nevertheless, modulating oxidative stress is still a significant challenge due to the lack of specific and modifiable targets. A central component that is integrated into several processes is glutathione, an essential thiol-based compound that is integrated into redox homeostasis. Objective: To establish the significance of glutathione and its availability in relation to HF. Methods: A comprehensive search strategy using PubMed, Embase, and Web of Science was developed. All human studies with patients with HF and animal studies with evidence of significant cardiac remodelling and available measurements of glutathione were included. Results: A total of 7656 articles were initially identified. Following first screening, 426 articles were selected for full assessment, out of which 217 reports were ultimately included in the analysis. There were 21 studies out of 25 that showed lower glutathione measures in patients with HF compared to controls, of which 18 reached statistical significance with an average reduction of 27.8 %. Regarding the animal evidence, 74.2 % and 79.3 % of the measurements in ischemic cardiomyopathy models and models with transverse aortic constriction, showed lower glutathione concentrations as compared to sham groups, respectively. Factors that positively influenced glutathione concentrations included all guideline-directed medical therapies, selenium, amlodipine, and N-acetylcysteine. Conclusion: Glutathione deficiency is a common finding in the context of HF. As it is a measurable and modifiable component with various biological targets, investigating the effects of optimizing its concentration in patients with HF should be pursued.
format Article
id doaj-art-3ec73f5dca184e3e9d562dd10192686e
institution DOAJ
issn 2667-1379
language English
publishDate 2025-06-01
publisher Elsevier
record_format Article
series Advances in Redox Research
spelling doaj-art-3ec73f5dca184e3e9d562dd10192686e2025-08-20T03:08:17ZengElsevierAdvances in Redox Research2667-13792025-06-011510013110.1016/j.arres.2025.100131Glutathione deficiency and heart failure: a systematic review of human and animal evidenceAli A. Al-Mubarak0Antonio Esquivel-Gaytan1Herman H.W. Silljé2Peter van der Meer3Nils Bomer4Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsCorresponding author: Dept. of Cardiology, University Medical Center Groningen, UMCG Post-zone AB43, PO Box 30.001 9700 RB Groningen, The Netherlands.; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsBackground: Oxidative stress is an important factor underlying several pathophysiological mechanisms in heart failure (HF). Nevertheless, modulating oxidative stress is still a significant challenge due to the lack of specific and modifiable targets. A central component that is integrated into several processes is glutathione, an essential thiol-based compound that is integrated into redox homeostasis. Objective: To establish the significance of glutathione and its availability in relation to HF. Methods: A comprehensive search strategy using PubMed, Embase, and Web of Science was developed. All human studies with patients with HF and animal studies with evidence of significant cardiac remodelling and available measurements of glutathione were included. Results: A total of 7656 articles were initially identified. Following first screening, 426 articles were selected for full assessment, out of which 217 reports were ultimately included in the analysis. There were 21 studies out of 25 that showed lower glutathione measures in patients with HF compared to controls, of which 18 reached statistical significance with an average reduction of 27.8 %. Regarding the animal evidence, 74.2 % and 79.3 % of the measurements in ischemic cardiomyopathy models and models with transverse aortic constriction, showed lower glutathione concentrations as compared to sham groups, respectively. Factors that positively influenced glutathione concentrations included all guideline-directed medical therapies, selenium, amlodipine, and N-acetylcysteine. Conclusion: Glutathione deficiency is a common finding in the context of HF. As it is a measurable and modifiable component with various biological targets, investigating the effects of optimizing its concentration in patients with HF should be pursued.http://www.sciencedirect.com/science/article/pii/S2667137925000128GlutathioneHeart failureGamma-glutamyl cycleRedox homeostasisOxidative stress
spellingShingle Ali A. Al-Mubarak
Antonio Esquivel-Gaytan
Herman H.W. Silljé
Peter van der Meer
Nils Bomer
Glutathione deficiency and heart failure: a systematic review of human and animal evidence
Advances in Redox Research
Glutathione
Heart failure
Gamma-glutamyl cycle
Redox homeostasis
Oxidative stress
title Glutathione deficiency and heart failure: a systematic review of human and animal evidence
title_full Glutathione deficiency and heart failure: a systematic review of human and animal evidence
title_fullStr Glutathione deficiency and heart failure: a systematic review of human and animal evidence
title_full_unstemmed Glutathione deficiency and heart failure: a systematic review of human and animal evidence
title_short Glutathione deficiency and heart failure: a systematic review of human and animal evidence
title_sort glutathione deficiency and heart failure a systematic review of human and animal evidence
topic Glutathione
Heart failure
Gamma-glutamyl cycle
Redox homeostasis
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S2667137925000128
work_keys_str_mv AT aliaalmubarak glutathionedeficiencyandheartfailureasystematicreviewofhumanandanimalevidence
AT antonioesquivelgaytan glutathionedeficiencyandheartfailureasystematicreviewofhumanandanimalevidence
AT hermanhwsillje glutathionedeficiencyandheartfailureasystematicreviewofhumanandanimalevidence
AT petervandermeer glutathionedeficiencyandheartfailureasystematicreviewofhumanandanimalevidence
AT nilsbomer glutathionedeficiencyandheartfailureasystematicreviewofhumanandanimalevidence