Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine

Department of Animal Sciences, University of Illinois, Urbana-Champaign, Urbana, Illinois, United States
Journal of Animal Science (Impact Factor: 2.11). 08/2007; 85(7):1712-8. DOI: 10.2527/jas.2006-835
Source: PubMed


Relative bioavailability and toxicity of N-acetyl-l-Cys (NAC) were evaluated in 9-d chick growth assays. The bioavailability of NAC relative to Cys was determined by feeding young chicks a highly purified crystalline AA diet singly deficient in Cys. Bio-availability estimates were obtained using standard slope-ratio methodology. N-Acetyl-l-cysteine was shown to be as effective as Cys in supporting chick growth, and was assigned a relative bioavailability value of 100%. To assess toxicity, a nutritionally adequate corn-soybean meal diet was supplemented with graded concentrations of NAC (isomolar to 10, 20, 30, or 40 g/kg of Cys, as-fed). When NAC supplied 10 or 20 g/kg of Cys, chick growth performance was unaffected, but NAC supplying 30 or 40 g/kg of Cys reduced (P < 0.05) BW gain by 13 and 34%, respectively, relative to the unsupplemented control diet. Only plasma-free NAC was substantially increased (P < 0.05) because of excess dietary NAC; plasma-free Cys was unaltered. We concluded that dietary NAC is efficacious in supplying Cys in support of chick growth, and only large excesses of NAC are growth depressing. Hence, the human clinical benefits of oral NAC likely result from its ability to deliver Cys safely and effectively to the portal circulation.

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Available from: Ryan N Dilger, Nov 26, 2015
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    • "Therefore, cystine and cysteamine were used in combination in this study to promote the synthesis of glutathione in oocytes from restraint-stressed mice. It has been reported that dietary NAC is efficacious in supplying cysteine in support of chick growth (Dilger & Baker 2007) and that NAC is available as a precursor for cysteine to support growth and protein (nitrogen) accretion in piglets administered a parenteral solution (Shoveller et al. 2006). However, several studies including the present study have observed little or no effect of NAC on oocyte quality when supplemented to IVM medium (Ali et al. 2003, Choe et al. 2010). "
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    ABSTRACT: Using the mouse model, we have tested the hypothesis that human IVF-associated psychological stress would impair oocyte developmental potential by causing oxidative stress (OS) and that antioxidant supplementation could overcome the adverse impact of stress-induced OS. Female mice were subjected to restraint stress (RS) for 24 h starting 24 h after eCG injection, to mimic the IVF-associated distress during the FSH-stimulation period. At the end of stress, mice were either sacrificed to recover oocytes for in vitro maturation (IVM) or injected with hCG and caged with males to observe in vivo development. The effect of antioxidants was tested in vitro by adding to IVM medium or in vivo by maternal injection immediately before RS. Measurements for total oxidative and antioxidant status, oxidative stress index, ROS and glutathione indicated that RS caused OS in mouse serum, ovary and oocytes. Whereas blastocyst rates and cell number per blastocyst decreased significantly in RS oocytes, antioxidant addition to IVM medium significantly improved their blastocyst development. Supplementation of cystine and cysteamine to IVM medium reduced the ROS level and aneuploidy while increasing glutathione synthesis and improving pre- and post-implantation development in RS oocytes. Furthermore, injection of stressed mice with antioxidant EGCG significantly improved blastocyst and post-implantation development of their oocytes. Together, results suggested that maternal psychological stress during the FSH-stimulation period of an IVF program may impair oocyte developmental potential by causing OS and that addition to IVM medium or maternal injection with antioxidants may overcome the detrimental effect of stress-induced OS.
    Preview · Article · Sep 2013 · Reproduction
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    • "However, NAC can also increase intracellular glutathione levels via increasing the levels of cellular cysteine (an amino acid which contains a thiol group) (Dilger and Baker, 2007). Free cysteine itself can function directly as a thiol reducing antioxidant and cysteine is essential in the synthesis of glutathione (GSH), a ubiquitously expressed tripeptide which is an important intracellular thiol-based antioxidant (Dilger and Baker, 2007; Ferreira and Reid, 2008; Medved et al., 2004): GSH participates in a variety of antioxidant pathways, including reduction of protein disulfides (Halliwell and Gutteridge, 2007). Therefore, the benefits of systemic NAC in dystrophic mdx mice and humans might also be a direct consequence of increasing cysteine and GSH levels in muscle. "
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    ABSTRACT: Oxidative stress has been implicated in the pathology of the lethal skeletal muscle disease Duchenne Muscular Dystrophy (DMD), and various antioxidants have been investigated as a potential therapy. Recently, treatment of the mdx mouse model for DMD with the antioxidant and cysteine and glutathione (GSH) precursor n-acetylcysteine (NAC) was shown to decrease protein thiol oxidation and improve muscle pathology and ex vivo muscle strength. This study further investigates the mechanism for the benefits of NAC on dystrophic muscle by administering L-2-Oxothiazolidine-4-Carboxylate (OTC) which also upregulates intracellular cysteine and GSH, but does not directly function as an antioxidant. We observed that OTC, like NAC, decreases protein thiol oxidation, decreases pathology and increases strength, suggesting that the both NAC and OTC function via increasing cysteine and GSH content of dystrophic muscle. We demonstrate that mdx muscle is not deficient in either cysteine or GSH and that these are not increased by OTC treatment. However, we show that dystrophic muscle of 12 week old mdx mice is deficient in taurine, a by-product of disposal of excess cysteine, a deficiency that is ameliorated by OTC treatment. These data suggest that in dystrophic muscles, apart from the strong association of increased oxidative stress and protein thiol oxidation with dystropathology, another major issue is an insufficiency in taurine that can be corrected by increasing the availability of cysteine. This study provides new insight into the molecular mechanism underlying the benefits of NAC in muscular dystrophy and supports the use of OTC as an alternative drug for potential clinical applications to DMD.
    Full-text · Article · Jul 2013 · The international journal of biochemistry & cell biology
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    • "In contrast, many properties of NAC make it a good candidate drug for AMD patients. NAC is both orally bioavailable and already approved for oral administration in the treatment of acetaminophen overdose.17,18 Topical administration of NAC may also be effective; there is evidence that topically applied NAC can penetrate to the posterior segment and protect cone cells from oxidative stress in mice.12 "
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    ABSTRACT: Oxidative stress induced retinal pigment epithelium (RPE) dysfunction is hypothesized to be fundamental in the pathogenesis of age-related macular degeneration (AMD). This study investigated whether vitamin C, vitamin C phosphate, vitamin E, propofol, betaxolol, and N-acetyl cysteine (NAC) protect human RPE cells from oxidative stress. ARPE-19 cells were pretreated with the compounds under investigation. The chemical oxidant tert-butyl hydroperoxide (t-BOOH) was used to induce oxidative stress. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Exposure to t-BOOH resulted in a dose- and time-dependent reduction in ARPE-19 cell viability. Compared with cells given t-BOOH alone, vitamin E and NAC pretreated cells had significantly improved viability, propofol and betaxolol pretreated cells had no significant difference in viability, and vitamin C and vitamin C phosphate pretreated cells had significantly reduced viability. Of the compounds studied, only vitamin E and NAC significantly mitigated the effects of oxidative stress on RPE cells. Because of their potential therapeutic value for AMD patients, these and other RPE protective compounds continue to merit further investigation.
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