The therapeutic potential of N-acetylcysteine across multiple organ systems: a narrative review.

Abstract: N‑acetylcysteine (NAC), a thiol‑containing acetylated derivative of L‑cysteine, has emerged as a multifunctional therapeutic agent beyond its classic role as a mucolytic and as an antidote for acetaminophen toxicity. As a glutathione precursor and direct free‑radical scavenger, NAC exhibits dual antioxidant and anti‑inflammatory effects, modulating key pathways such as Nrf2 and NF‑κB and influencing cellular redox homeostasis. This comprehensive review synthesizes preclinical and clinical evidence for NAC's effects across multiple organ systems. In the respiratory system, NAC improves mucus clearance, reduces exacerbations in COPD, and shows variable benefits in idiopathic pulmonary fibrosis, with emerging precision‑medicine approaches exploring genotype‑guided therapy. In cardiovascular settings, NAC demonstrates endothelial‑protective properties, enhanced nitric oxide bioavailability, and potential to reduce perioperative oxidative injury, though large‑scale trials report mixed impacts on mortality and arrhythmia rates. Renal studies reveal protective effects against contrast‑induced nephropathy and perioperative acute kidney injury by attenuating oxidative and inflammatory markers. Within the central nervous system, NAC has shown neuroprotective properties in vitro and in vivo, including reduced oxidative stress, modulated glutamate transport, and partial mitigation of neurodegenerative processes, although clinical results remain inconsistent. Its safety profile is generally favorable, with mild gastrointestinal effects being the most common adverse events. Collectively, these findings highlight NAC as a promising adjunctive therapy with broad biological plausibility. However, variability in dosing, bioavailability, and patient selection underscores the need for further mechanistic research and well‑designed randomized trials to establish its long‑term clinical utility.