The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress

Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitouscellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptideglutathione (GSH), which is synthesized and maintained at high concentrations in all cells, isone of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine(NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH,has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol)poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins,thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As anantidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxificationprocess. More recently, improved knowledge of the mechanisms by which NAC actshas expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasisof glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impairedglutamate homeostasis. This narrative review provides an overview of the most relevant andrecent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophenpoisoning, disorders of the central nervous system (chronic neuropathic pain, depression,schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-inducednephropathy, and ophthalmology (retinitis pigmentosa).