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Cited by 470

The DOI matches its Crossref record; 228 of the 228 references it cites were found in a registry or an index.

The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species

Open access
Pedre, Brandán, Barayeu, Uladzimir, Ezeriņa, Daria, Dick, Tobias P.·2021·Pharmacology & Therapeutics
DOI 10.1016/j.pharmthera.2021.107916
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Abstract

Initially adopted as a mucolytic about 60 years ago, the cysteine prodrug N-acetylcysteine (NAC) is the standard of care to treat paracetamol intoxication, and is included on the World Health Organization's list of essential medicines. Additionally, NAC increasingly became the epitome of an "antioxidant". Arguably, it is the most widely used "antioxidant" in experimental cell and animal biology, as well as clinical studies. Most investigators use and test NAC with the idea that it prevents or attenuates oxidative stress. Conventionally, it is assumed that NAC acts as (i) a reductant of disulfide bonds, (ii) a scavenger of reactive oxygen species and/or (iii) a precursor for glutathione biosynthesis. While these mechanisms may apply under specific circumstances, they cannot be generalized to explain the effects of NAC in a majority of settings and situations. In most cases the mechanism of action has remained unclear and untested. In this review, we discuss the validity of conventional assumptions and the scope of a newly discovered mechanism of action, namely the conversion of NAC into hydrogen sulfide and sulfane sulfur species. The antioxidative and cytoprotective activities of per- and polysulfides may explain many of the effects that have previously been ascribed to NAC or NAC-derived glutathione.

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Metadata

Authors
Pedre, B., Barayeu, U., Ezeriņa, D., & Dick, T. P.
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
2021-12
Volume
228
Pages
107916
ISSN
0163-7258 (ISSN-L)
DOI
10.1016/j.pharmthera.2021.107916
OpenAlex
W3173942724
Cited by
470
References
228
FWCI
19.78
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. https://app.cochat.ai/papers/10.1016/j.pharmthera.2021.107916
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Pedre, B., Barayeu, U., Ezeriņa, D., & Dick, T. P. (2021). The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacology & Therapeutics. https://doi.org/10.1016/j.pharmthera.2021.107916

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.