N-Acetylcysteine is a Highly Available Precursor for Cysteine in the Neonatal Piglet Receiving Parenteral Nutrition

ArticleinJournal of Parenteral and Enteral Nutrition 30(2):133-42 · March 2006with34 Reads
DOI: 10.1177/0148607106030002133 · Source: PubMed
Cysteine (CYS) is accepted as an indispensable amino acid for infants receiving parenteral nutrition (PN), and CYS is unstable in solution. Thus, developing a method to supply CYS in PN for neonates is needed. N-acetyl-L-cysteine (NAC) is stable in solution and safe for use in humans; therefore, NAC may be a means of supplying parenteral CYS. We determined the bioavailability of NAC in intravenously (IV)-fed piglets randomized to 1 of 4 diet treatments, each supplying 0.3 g/kg/d methionine and either 0.2 g/kg/d CYS (CON), 0 NAC (zeroNAC), 0.13 NAC (lowNAC), or 0.27 g/kg/d NAC (highNAC). Piglets (2 days old; 1.8 kg, n = 20) were surgically implanted with femoral and jugular catheters. On day 3 postsurgery, test diets were initiated and continued until day 8. Piglets were weighed daily. Blood was sampled 6 hours before test diet initiation and at 0, 6, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours. Urine was collected on ice in 24-hour sample periods. Total mean weight gain was not different between groups; however, average daily gain in the zeroNAC and lowNAC groups declined significantly (p < .05) over the 5-day treatment period. Nitrogen retention was similar between the CON and highNAC groups, both were higher than the lowNAC group, and the zeroNAC treatment produced the lowest nitrogen retention. NAC percent retention was not different between lowNAC and highNAC and was 85.4% and 82.6%, respectively. Plasma NAC was higher in highNAC than lowNAC (p < .05). These data demonstrate that NAC is available as a precursor for CYS to support growth and protein (nitrogen) accretion in piglets administered a parenteral solution.
    • "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). "
    [Show abstract] [Hide abstract] 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.
    Article · Sep 2013
    • "Cys, which participates in a variety of metabolic pathways involving Met, glutathione, 34 coenzyme A, and taurine (Stipanuk, 2004). Studies suggest Cys should be considered a 35 conditionally indispensable AA (Shoveller et al., 2006) contingent on Met status of the 36 animal. However, dietary supplementation of Cys is complicated because its free 37 sulfhydryl group is capable of spontaneous oxidation, resulting in product instability. "
    [Show abstract] [Hide abstract] ABSTRACT: 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.
    Full-text · Article · Aug 2007
  • [Show abstract] [Hide abstract] ABSTRACT: Animal studies have shown that several methionine (Met) and cysteine (Cys) analogs or precursors have L-Met- and L-Cys-sparing activity. Relative oral bioavailability (RBV) values, with the L-isomer of Met and Cys set at 100% (isosulfurous basis), are near 100% for D-Met for animals but only about 30% for humans. Both the OH and keto analogs of Met have high RBV-sparing values, as does N-acetyl-L-Met (the D-isomer of acetylated Met has no bioactivity). L-Homocysteine has an RBV value of about 65% for Met sparing in rats and chicks, but D-homocysteine has little if any Met-sparing activity. S-Methyl-L-Met can partially spare Met, but only when fed under dietary conditions of choline/betaine deficiency. Relative to L-Cys, high RBV values exist for L-cystine, N-acetyl-L-Cys, L-homocysteine, L-Met, and glutathione, but D-cystine, the keto analog of Cys, L-cysteic acid, and taurine have no Cys-sparing activity. l-2-Oxothiazolidine-4-carboxylate has an RBV value of 75%, D-homocysteine 70%, and DL-lanthionine 35% as Cys precursors. Under dietary conditions of Cys deficiency and very low inorganic sulfate (SO4) ingestion, dietary SO4 supplementation has been shown to reduce the Cys requirement of several animal species as well as humans. Excessive ingestion of Met, Cys, or cystine has also been studied extensively in experimental animals, and these sulfur amino acids (SAA) are well established as being among the most toxic of all amino acids that have been studied. Even though Cys and its oxidized product (cystine) are equally efficacious at levels at or below their dietary requirements for maximal growth, Cys is far more toxic than cystine when administered orally in the pharmacologic dosing range. Isosulfurous (excess) levels of cystine, N-acetyl-L-Cys, or glutathione are far less growth depressing than L-Cys when 6 to 10 times the minimally required level of these SAA compounds are fed to chicks.
    Article · Jul 2006
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