Cystein in der parenteralen Ernährung: Vergleichende Studien über N-Acetylcystein und NN-Diacetylcystin am Modell der Ratte

Abstract

In der vorliegenden Arbeit wurde untersucht, ob das stabilere N-N-Diacetylcystin (DAC) ersatzweise für N-Acetylcystein (AcCYS) als Cysteinquelle in der parenteralen Ernährung geeignet ist. In vitro wurde die Freisetzung von Cystein (CYS) in der Rattenleber gemessen, Km und Vmax wurden bestimmt. Junge Ratten wurden 15 Tage parenteral ernährt. Es wurden 3 methioninarme Lösungen getestet. Gruppe I (n = 4) erhielt AcCYS, Gruppe II (n = 6) DAC und Gruppe III (n = 6) Glycin. Gewichtszunahme, Stickstoffbilanz, Plasma-Aminosäuren und Aminosäurenausscheidung im Urin dienten als Bewertungskriterien für die Verfügbarkeit von CYS aus den getesteten Derivaten in vivo. Die Ergebnisse zeigen, daβ DAC kei geeigneter Ersatz für AcCYS in der parenteralen Ernährung ist.

Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation

“…The ESPGHAN/ESPEN/ESPR Guidelines also recommend the administration of the semiessential amino acid cysteine [ 2 , 4 ] to newborn and preterm infants, but they do not mention the best source to be used (cysteine-HCl or N -acetylcysteine) [ 2 , 3 ]. Due to its good solubility and stability in PPN and its ability to be easily transformed into cysteine [ 6 , 8 ], most amino acid mixtures for pediatric patients contain N -acetylcysteine (NAC) although its bioavailability is of only 50% [ 3 ].…”

“…It is known that NAC is oxidized to its dimer N , N -diacetylcystine (DAC) [ 6 , 7 ]. When given orally, this reaction is easily reversible as DAC is reduced to NAC and further to cysteine during its passage through the small intestine.…”

“…When given orally, this reaction is easily reversible as DAC is reduced to NAC and further to cysteine during its passage through the small intestine. This is the missing step when NAC is administered intravenously [ 6 , 8 ]. Therefore, oxidized NAC stays unavailable for cysteine delivery in PPN.…”

“…A soluble precursor is N -acetylcysteine (NAC), the acetylated form of cysteine [ 5 ]. In vivo, it is easily converted into bioavailable cysteine after catalysis by an acylase [ 6 , 7 ]. Therefore, cysteine is commonly supplemented by means of administration of a PPN for preterm infants containing an amino acids (AA) mixture including 0.7 g/L of NAC (equivalent to 0.52 g/L of cysteine) (Aminoven ® Infant 10%, Fresenius Kabi AG, Germany; Aminoplasmal ® Paed 10%, B. Braun Medical AG, Germany; Aminopaed ® 10%, Baxter International, Deerfield, IL, USA).…”

“…DAC is soluble and more stable in PPN solution than NAC. However, it is converted 30 times slower into cysteine when given intravenously than after oral administration where DAC is reduced by cystine-reductase during its passage through the small intestine [ 6 ].…”