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Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits
- Source :
- Pharmacology & Therapeutics. 141:150-159
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More recently, however, a wide range of clinical studies have reported on the use of NAC as an antioxidant, most notably in the protection against contrast-induced nephropathy and thrombosis. The results from these studies are conflicting and a consensus is yet to be reached regarding the merits or otherwise of NAC in the antioxidant setting. This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an "antioxidant". Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.
- Subjects :
- Pharmacology
Antioxidant
NAPQI
medicine.medical_treatment
Context (language use)
Glutathione
Antioxidants
Acetylcysteine
Acetaminophen
chemistry.chemical_compound
Mechanism of action
chemistry
Biochemistry
medicine
Animals
Humans
Glutathione disulfide
Prodrugs
Pharmacology (medical)
medicine.symptom
medicine.drug
Subjects
Details
- ISSN :
- 01637258
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- Pharmacology & Therapeutics
- Accession number :
- edsair.doi.dedup.....6f0d38874978f662101ca993e01be5e5