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

Author(s):

Ganesh Raghu, Michael Berk, Peter A. Campochiaro, Hartmut Jaeschke, Giancarlo Marenzi, Luca Richeldi, Fu-Qiang Wen, Ferdinando Nicoletti and Peter M. A. Calverley*   Pages 1 - 23 ( 23 )

Abstract:


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).

Keywords:

Antioxidant, glutathione, N-acetylcysteine, mucolytic, oxidative stress, acetaminophen, treatment, psychiatry.

Affiliation:

Division of Pulmonary, Sleep & Critical Care Medicine, Department of Medicine; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Centro Cardiologico Monzino, I.R.C.C.S, Milan, Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli IRCCS, Rome, Department of Medicine, West China Hospital of Sichuan University, Chengdu, Department of Physiology and Pharmacology, University of Rome "Sapienza", Rome, Italy; IRCCS Neuromed, Pozzilli, Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool



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