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 ubiquitous
cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide
glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is
one 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 an
antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification
process. More recently, improved knowledge of the mechanisms by which NAC acts
has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis
of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired
glutamate homeostasis. This narrative review provides an overview of the most relevant and
recent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophen
poisoning, disorders of the central nervous system (chronic neuropathic pain, depression,
schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-induced
nephropathy, and ophthalmology (retinitis pigmentosa).