The mechanism of action of N-acetylcysteine (NAC): The emerging role of H 2 S and sulfane sulfur species.
Level 5 - mechanism / opinion, no new human data
Narrative review evaluating proposed biochemical mechanisms without primary human data.
PubMed 34171332 · doi:10.1016/j.pharmthera.2021.107916
What was done
This narrative review evaluated the proposed biochemical mechanisms of action of N-acetylcysteine (NAC). The authors reviewed traditional explanations—specifically disulfide bond reduction, reactive oxygen species (ROS) scavenging, and glutathione precursor activity—and examined evidence for an alternative pathway involving NAC metabolism into hydrogen sulfide (H2S) and sulfane sulfur species.
What was found
The abstract provides no empirical numbers or quantitative metrics. It reports that conventional mechanisms (direct ROS scavenging and glutathione synthesis) cannot be generalized to explain NAC's effects across most settings. Instead, the generation of H2S and sulfane sulfur species (per- and polysulfides) is highlighted as an alternative mechanism explaining cytoprotective and antioxidative properties historically attributed directly to NAC or glutathione.
Why it matters
This review reframes the understanding of NAC beyond simple direct antioxidant scavenging, emphasizing reactive sulfur species as potential mediators of its biological activity in cellular and experimental models.
Limits
The paper is a narrative mechanistic overview and does not report systematic search methods, clinical trials, or new primary experimental data. No numerical findings or effect sizes are provided in the abstract.
Cited by
- context N-acetylcysteine (NAC) functions as an antioxidant and recycles the glutathione peroxidase system to mitigate oxidative stress.