Amino Acid Solutions for Premature Neonates During the First Week of Life: The Role of N‐Acetyl‐L‐Cysteine and N‐Acetyl‐L‐Tyrosine

Goudoever, Johannes B. van; Sulkers, Esther; Timmerman, Michelle; Huijmans, J. G. M.; Langer, Klaus; Carnielli, Virgilio P.; Sauer, Pieter J. J.

doi:10.1177/0148607194018005404

Cited by 67 publications

(45 citation statements)

References 31 publications

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“…Of interest, the use of NAC in preterm infants during the first week of life has not been shown to reduce the incidence of bronchopulmonary dysplasia (18,19), another morbidity of premature birth that is associated with hyperoxic exposure. Preterm infants may not effectively deacetylate NAC to cysteine, which is necessary for the molecule to function as a precursor for glutathione (20).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

Kwak

Gauda

2006

Pediatr Res

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Hyperoxia, during development in rats, results in hypoxic chemosensitivity ablation, carotid body hypoplasia, and reduced chemoafferents. We hypothesized that hyperoxia increases reactive oxygen species (ROS) in cell bodies of chemoafferents. Organotypic slices of petrosal-nodose ganglia from rats at day of life (DOL) 5-6 and 17-18 were exposed to 8%, 21%, or 95% O 2 for 4 h in the presence or absence of the ROS-sensitive fluorescent indicator, CM-H 2 DCFDA, and propidium iodide was used to determine the relationship between cell death and oxygen tension. In tissue slices from DOL 5-6 rats, fluorescence intensity was 182.5 Ϯ 2.9 for hypoxia, 217.5 Ϯ 3.3 for normoxia, and 336.6 Ϯ 3.8 for hyperoxia, (mean Ϯ SEM, p Ͻ 0.001, ANOVA). Normoxia increased ROS levels by 19.2% from hypoxia (p Ͻ 0.01) with a further increase of 54.8% from normoxia to hyperoxia (p Ͻ 0.001). In tissue slices from DOL 17-18 rats, ROS levels increased with increasing oxygen tension but were less than in younger animals (p Ͻ 0.01, ANOVA). The antioxidants, NAC and TEMPO-9-AC, attenuated ROS levels and cell death. Electron microscopy demonstrated that hyperoxia damages the ultrastructure within petrosal ganglion neurons. Hyperoxic-induced increased levels of ROS in petrosal ganglion neurons may contribute to loss of hypoxic chemosensitivity during early postnatal development. N umerous studies in mammalian species support a role for peripheral arterial chemoreceptors in stabilizing ventilation at a critical period during early postnatal development, which establishes rhythmogenesis that is sustained throughout life (1,2). The components of the peripheral arterial chemoreceptors are found within the carotid body that is located in the bifurcation of the carotid artery and consists of three major neuronal components that include: 1) type I chemosensory cells, also known as glomus cells, which contain neurotransmitters and autoreceptors; 2) type II cells, which are similar to supportive glial cells; and 3) chemoafferent nerve fibers from the carotid sinus nerve, a branch of the IX cranial nerve, with cell bodies in the petrosal ganglion (PG) (3,4).Exposure to chronic hyperoxia, during the first weeks of postnatal development, depresses ventilatory responses to subsequent acute hypoxia in newborn animals and in premature infants (5-7). Hyperoxic exposure in newborn rat pups is cytotoxic to peripheral arterial chemoreceptors as evidenced by hypoplasia of the carotid body and a 41% reduction in the number of chemoafferent neurons (8). The mechanisms leading to cytotoxic changes in the carotid body and the reduction in chemoreflexes after hyperoxicexposure during early postnatal development are unknown. In other model systems, hyperoxia is associated with increased production of ROS, including superoxide, hydroxyl radical, and hydrogen peroxide, which can contribute to cellular damage via lipid peroxidation, enzyme inactivation, and protein and nucleic acid oxidation, resulting in apoptosis or necrosis (9). Using a novel ex vivo organotypic s...

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Section: Discussionmentioning

confidence: 99%

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

Kwak

Gauda

2006

Pediatr Res

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“…N-acetyl-tyrosine, for example, has been included in one of the commercially available pediatric amino acid solutions, TrophAmine (McGaw Inc., Irvine, CA, U.S.A.) (13). Unfortunately, N-acetyl-tyrosine has been shown to be poorly used in the parenterally fed piglet, which excreted 65% of intake (14), and in the human neonate who also has demonstrated poor utilization through the excretion of large quantities of the derivative (13,(15)(16)(17). In contrast, there is evidence that dipeptides of tyrosine can serve as a soluble source of tyrosine in pigs (14,18,19), primates (20), and adult humans (21)(22)(23)(24)(25).…”

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confidence: 99%

The Effect of Graded Intake of Glycyl-l-Tyrosine on Phenylalanine and Tyrosine Metabolism in Parenterally Fed Neonates with an Estimation of Tyrosine Requirement

et al. 2001

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Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 Ϯ 38 kJ⅐kg -1 ⅐d -1 ) and protein (2.4 Ϯ 0.4 g⅐kg -1 ⅐d -1 ) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-13 C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO 2 (F 13 CO 2) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg⅐kg , respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate. (Pediatr Res 49: 111-119, 2001) Abbreviations TPN, total parenteral nutrition FCO 2 , breath carbon dioxide production F 13 CO 2 , breath 13 CO 2 production GT, glycyl-L-tyrosine Nearly three decades ago, Snyderman (1) suggested that the neonate requires a preformed source of tyrosine. Presently, the main impediment to meeting total aromatic amino acid requirements in the parenterally fed neonate is the poor solubility of tyrosine (0.453 g/L in H 2 O at 25°C) (2), limiting its inclusion in parenteral amino acid solutions to Ͻ1% of total amino acids. When compared with neonatal reference proteins such as human milk or human fetal tissue, which contain approximately equal quantities of phenylalanine and tyrosine (3.7-4.1 and 2.9 -4.6 g/100 g protein, respectively) (3-5), the levels provided by these synthetic nutrient solutions appear grossly inadequate. To circumvent this problem, increased phenylalanine has been included in some solutions in hope that the neonate will endogenously hydroxylate sufficient phenylalanine to tyrosine to meet total aromatic amino acid needs. However, elevated plasma phenylalanine levels have been observed with this approach (6 -11), even though it has been shown that increased phenylalanine intake is associated with an absolute greater rate of in vivo phenylalanine hydroxylation (12).Derivatives of tyrosine have also been investigated as soluble precursors of tyrosine. N-acetyl-tyrosine, for example, has been included in one of the commercially available pediatric amino acid solutions, T...

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“…For these amino acids the inclusion of their precursors, phenylalanine and methionine, does not result in higher plasma tyrosine and cyst(e)ine concentrations. The mixture does contain some N-acetyl-L-tyrosine but the bioavailability of this soluble tyrosine salt is less than optimal Van Goudoever et al 1994). Moreover, cyst(e)ine can be provided as the HCl salt, remembering that it is likely to cause metabolic acidosis (Laine et al 1991).…”

Section: Improving the Composition Of Parenteral Amino Acid Mixturesmentioning

confidence: 99%

“…Moreover, cyst(e)ine can be provided as the HCl salt, remembering that it is likely to cause metabolic acidosis (Laine et al 1991). It also can be provided as the poorly-bioavailable N-acetyl-L-cyst(e)ine (Van Goudoever et al 1994). Dipeptides containing the amino acids are now available and, in theory, should be the ideal source of tyrosine and cyst(e)ine.…”

Section: Improving the Composition Of Parenteral Amino Acid Mixturesmentioning

confidence: 99%

Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials

Heird

2005

Proc. Nutr. Soc.

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Studies of biochemical homeostasis and/or body growth have been included as outcome variables in most nutrition trials in paediatric patients. Moreover, these outcome variables have provided important insights into the nutrient requirements of infants and children, and continue to do so. Examples of the value of such studies in improving parenteral nutrition, in defining essential fatty acid metabolism and requirements of infants and in defining the protein and energy needs of low-birth-weight infants are discussed. Data from such studies have helped to define the mechanism of metabolic acidosis and hyperammonaemia associated with the use of early crystalline amino acid mixture and, hence, how to prevent these disorders. Such studies have allowed the development of parenteral amino acid mixtures that circumvent grossly abnormal plasma concentrations of most amino acids and appear to be utilized more efficiently. These studies have also helped define micronutrient requirements, including requirements for several such nutrients that had not been previously recognized as essential (e.g. Cr, Se, Mo, α-linolenic acid). Studies of body growth have been particularly valuable in defining the nutritional requirements of low-birth-weight infants. Finally, studies of metabolic homeostasis coupled with more sophisticated metabolic studies have provided considerable insight into the metabolism of the essential fatty acids, linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3). Although such studies have not defined the amount of the longer-chain PUFA synthesized from each of these essential fatty acids, i.e. arachidonic acid (20:4n-6) and DHA (22:6n-3), they have shown that the rates of conversion are extremely variable from infant to infant, suggesting a possible explanation of why some studies show developmental advantages from intake of these fatty acids while others do not.

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Amino Acid Solutions for Premature Neonates During the First Week of Life: The Role of N‐Acetyl‐L‐Cysteine and N‐Acetyl‐L‐Tyrosine

Cited by 67 publications

References 31 publications

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

The Effect of Graded Intake of Glycyl-l-Tyrosine on Phenylalanine and Tyrosine Metabolism in Parenterally Fed Neonates with an Estimation of Tyrosine Requirement

Biochemical homeostasis and body growth are reliable end points in clinical nutrition trials

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