N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency

Abstract

Glutathione (GSH) deficiency is associated with numerous pathological conditions. Administration of N-acetylcysteine (NAC), a cysteine prodrug, replenishes intracellular GSH levels. NAC, best known for its ability to counter acetaminophen toxicity, is a safe, well-tolerated antidote for cysteine/GSH deficiency. NAC has been used successfully to treat GSH deficiency in a wide range of infections, genetic defects and metabolic disorders, including HIV infection and COPD. Over two-thirds of 46 placebo-controlled clinical trials with orally administered NAC have indicated beneficial effects of NAC measured either as trial endpoints or as general measures of improvement in quality of life and well-being of the patients.

N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial

“…We did not observe any severe side effects, such as anaphylactoid reaction, and the prevalence of possible NAC adverse drug reactions was similar in both study groups. [16][17] It is in line with the study by Barkholt et al 18 in which no infusionrelated toxicity or side effects were reported following administration of high doses of parenteral NAC in hematopoietic SCT patients. We used the injectable form of NAC because oral administration of 100 mg/kg/day of NAC in the form of 200 or 600 mg tablets seemed to be unfeasible.…”

“…These side effects abate shortly after NAC discontinuation or administration rate reduction. 16,17 In a study using high doses of parenteral NAC for early liver toxicity of allogeneic hematopoietic SCT, no infusion-related toxicity or side effects were reported. 18,19 Few animal and clinical studies exist on the efficacy of NAC for prevention of radiation-induced OM and they have shown promising results in reducing OM severity using a topical formulation.…”

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

“…(Glutathione interacts with GCL allosterically to inhibit its activity (Richman and Meister 1975)). An efficient way to achieve this, without increasing protein intake per se, is to supplement with N-acetylcysteine (NAC), a well-absorbed and chemically stable compound that is rapidly cleaved to liberate free cysteine soon after it is absorbed (Atkuri et al 2007;Dodd et al 2008). (Cysteine per se is too unstable to be employed as a concentrated supplement, and the cystine which it readily gives rise to is poorly absorbed.)…”

Effect of N-acetylcysteine on pulmonary cell death in a controlled hemorrhagic shock model in rats

“…compound with antioxidant and anti-inflammatory properties, exhibiting effects on microcirculation 12 . NAC acts directly as an antioxidant, by deactivating reactive oxygen species, or indirectly, by replacing intracellular glutathione stores.…”