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

Anna K. Shoveller, PhD^*, Janet A. Brunton, PhD, Ortrud Brand^¶, Paul B. Pencharz, MD, PhD^*,,,|| and Ronald O. Ball, PhD^*,,||

From the ^* Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada; The Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics and ^|| Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; and^¶ Fresenius Kabi, Bad Homburg, Germany

Correspondence: Ronald O. Ball, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada T6G 2P5. Electronic mail may be sent to ron.ball{at}ualberta.ca.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

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