Abstract
Preterm infants have diminished antioxidant defenses. Glutathione (GSH), the main intracellular antioxidant, increases upon amino acid (AA) administration in preterm infants, without an accompanying rise of the fractional synthesis rate of GSH (FSRGSH) This study investigated the mechanism behind this increased GSH concentration by determining GSH synthesis in the first days after birth using stable isotope techniques in very low-birth-weight (VLBW) infants receiving i.v. AAs. Advanced oxidized protein products (AOPPs) were determined to quantify oxidative stress. Eighteen infants (birth weight 989 ± 241 g, gestational age of 276/7 ± 14/7 weeks) were studied either on postnatal day 1 or 2 (7 or 31 h postnatally, respectively). Concentration of GSH increased with postnatal age (1.45 ± 0.48 mM versus 1.99 ± 0.40 mM, p = 0.019). FSRGSH was not significantly different, but the absolute synthesis rate of GSH (ASRGSH) tended to be higher in the infants studied on day 2 [8.1 ± 2.7 mg/(kg · d) versus 10.6 ± 2.4 mg/(kg · d), p = 0.054]. AOPP concentrations were not different between groups. In conclusion, GSH concentration in VLBW infants increases significantly after birth. A concomitant increased synthesis rate was not found, suggesting that GSH consumption decreases upon AA administration.
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The sudden increase in oxygen pressure accompanying birth results in increased formation of reactive oxygen species (ROS). If birth is marked by a period of ischemia followed by reoxygenation (e.g. asphyxia), ROS formation is further augmented through the hypoxanthine-xanthine oxidase pathway (1,2). In addition, preterm infants are frequently exposed to ventilation with high concentrations of oxygen, further adding up to this ROS formation (3). Therefore, newborn infants, and especially preterm infants, are exposed to increased levels of ROS.
In term infants, antioxidant defenses are sufficiently present at birth to counteract this hyperoxic challenge, because antioxidant enzymes mature during late gestation (4). Several weeks before birth, parallel with the rapid rise in lung surfactant, there is a 150–200% increase in superoxide dismutase and glutathione peroxidase (5,6). In addition, the transfer of several antioxidants across the placenta increases during the last days of pregnancy (4). Thus, when an infant is born premature, most of its antioxidant defense mechanisms function suboptimally at birth. The resulting redox imbalance promotes oxidative stress, which is thought to be instrumental in the pathogenesis of the so-called “Oxygen Radical Disease in Neonatology.” The latter comprises diseases such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL) (7).
Glutathione (GSH) is the most important intracellular antioxidant. GSH is a tripeptide consisting of the amino acids (AA) glutamate, cysteine, and glycine. It is synthesized in virtually every tissue but is mainly produced in liver and erythrocytes with erythrocytic concentrations being in the millimolar range (8). Erythrocytes are suggested to function as antioxidant defense by being a physiologic source of GSH and by taking up ROS (9,10).
Although preterm infants show diminished availability of other components of the antioxidant defense systems, the GSH concentrations in cord blood of preterm infants at birth exceed those of term infants (9,11,12). GSH concentrations, however, fall rapidly after birth in preterm infants. Recently, we demonstrated that administering AAs to preterm infants from birth onward results in higher GSH concentrations on day 2, compared with levels found in infants receiving glucose only (13). The purpose of this study was to reveal the mechanism behind the increased availability of GSH with early administration of AAs. We, therefore, hypothesized that GSH synthesis is already up-regulated very shortly after birth, resulting in the increased GSH concentration on postnatal day 2. In this study, we conducted a stable isotope technique to determine glutathione synthesis rates in the first days after birth in infants receiving AAs directly after birth. With stable isotope techniques, we are able to calculate the fractional synthesis rate (FSRGSH), which is the fraction of the total intraerythrocytic GSH pool that is renewed per unit of time, and the absolute synthesis rate (ASRGSH), which is the absolute amount of GSH that is produced per unit of time.
In addition, we quantified oxidative stress by determining concentrations of the advanced oxidized protein products (AOPP), first described as a marker for protein oxidation in uremic patients (14). Hypoxic preterm infants showed higher plasma concentrations of AOPP than normoxic preterm infants and concentrations correlated with plasma levels of hypoxanthine, which is considered a reliable marker of oxidative stress (15).
SUBJECTS AND METHODS
This study was designed as a prospective observational clinical trial in which infants were randomized to be studied either on postnatal day 1 (early group) or 2 (late group). Because this study was performed on subsequent days, different infants were used for the tracer infusion study either early or late after birth, because of the required washout time of [1-13C]glycine.
The study was performed at the neonatal intensive care unit of the Erasmus MC–Sophia Children's Hospital, Rotterdam, the Netherlands. The study was investigator initiated with no funding from industry. The Erasmus MC Medical Ethical Review Board approved the protocol, and informed written parental consent was obtained before the study.
Subjects.
Preterm infants with a birth weight <1500 g, who had an indwelling arterial catheter for blood sampling and who were completely dependent on parenteral nutrition for the first 2 d of life, were eligible for this study. Exclusion criteria included receiving erythrocyte transfusions during or before the study; known congenital abnormalities; chromosome defects; and metabolic, endocrine, renal, or hepatic disorders.
Patients received glucose and 2.4 g of AA/(kg · d) (Primene 10%, Baxter, Clintec Benelux N.V., Brussels, Belgium) i.v., starting within 2 h after birth. AAs and glucose solutions were infused constantly without interruptions during the study. The AA solutions did not contain riboflavins, which are known to generate H2O2 when exposed to light (16). Lipids were not administered until the end of the study period.
Birth weight, gestational age, birth weight Z-scores, antenatal corticosteroid usage, and severity of illness at entry of the study by means of Apgar and CRIB (clinical risk index for babies) scores (17) were recorded for all infants. Furthermore, blood gases, plasma AA concentrations, dependence on supplemental oxygen [expressed as the median (min–max) FiO2 from birth until the end of the study], caloric intake, and AA intake were recorded.
Tracer infusion protocol.
Patients received a primed (40 μmol/kg), continuous [20 μmol/(kg · h)] infusion of [1-13C]glycine during 6 h either on day 1 (early) or on day 2 (late). [1-13C]Glycine (99% enriched, sterility and pyrogenicity tested) was purchased from Cambridge Isotope Laboratories (Andover, MA) and was diluted with a 0.9% saline solution by the hospital's pharmacy after which it was again tested for sterility and pyrogenicity. Tracers were infused with a Perfusor fm infusion pump (B. Braun Medical B.V., Oss, the Netherlands) along the same infusion route as the parenterally administered nutrients. Blood was sampled from an indwelling arterial catheter after 4, 5, and 6 h and collected in microtainers containing EDTA to quantify FSRGSH in erythrocytes.
Sample analyses.
Blood samples were immediately put on melting ice, after which they were centrifuged at 3500 × g for 10 min at 4°C. The plasma fraction was removed and stored separately for measurement of oxidative stress markers. The lower layer, containing primarily erythrocytes, was reconstituted to its original volume with ice-cold distilled water. The plasma fraction and cell fraction were subsequently stored at −80°C until further analysis.
Glutathione enrichments and concentration.
Enrichments of GSH and its precursor glycine as well as GSH concentrations were determined to calculate fractional and absolute synthesis rates. For this purpose, a recently described technique, based on a LC-Isolink interface (Thermo Electron, Bremen, Germany) coupled to a Delta XP isotope ratio mass spectrometer (Thermo Electron, Bremen, Germany) (LC-IRMS), was used (18). This highly sensitive method requires only a very small sample volume and does not require derivatization.
The concentration of GSH in human blood erythrocytes was measured by LC-IRMS using an internal standard method as described previously (18).
Calculations.
FSRGSH represents the fraction of the total intraerythrocytic GSH pool that is renewed per unit of time and is expressed as %/d.
equation
where E stands for enrichment expressed as mole percent excess (MPE). The numerator (product) of this equation represents the hourly increase in [1-13C]glycine bound GSH as calculated from the increase in enrichment between 4 and 6 h of infusion. The denominator (precursor) represents the intraerythrocytic 1-13C enrichment of free glycine at isotopic steady state. A steady-state plateau was defined as an insignificant change in time in intraerythrocytic enrichment.
Subsequently, the intravascular ASRGSH, which represents the absolute amount of GSH that is produced per unit of time [mg/(kg · d)], can be calculated using the following equation:
where conc. is GSH concentration in mmol/L packed erythrocytes, 307 is the molecular weight of GSH, ht is hematocrit, and 0.075 is the estimated circulating volume in a preterm neonate, expressed as L/kg.
Amino acid concentrations.
Plasma concentrations of direct GSH precursors glutamate, glycine, and cysteine (measured as cystine), and indirect precursors glutamine, methionine, and serine, were determined with a Biochrom 30 amino acid analyzer, using ninhydrin detection (Biochrom Ltd., Cambridge, England).
Plasma markers of oxidative stress.
We measured AOPP in plasma by the spectrophotometric assay described by Witko-Sarsat et al. (14). The AOPP were calibrated with chloramine-T solutions that absorb at 340 nm in the presence of potassium iodide. Because the absorbance of chloramine-T at 340 nm is linear up to 100 μM, AOPP concentrations were expressed as μmol/L chloramine-T equivalents.
Statistics.
Statistical analyses were performed using SPSS v14.0 (SPSS Inc., Chicago, IL) and Graph Prism v4 (GraphPad Software Inc., San Diego, CA). Data are expressed as means ± SD or as medians (min–max). Primary outcome of this study was the glutathione fractional synthesis rate. Power calculation shows that, to detect a difference in FSRGSH of 10%/d and a SD of 6% [based on our earlier study (13)] with an α of 0.05 and a power of 0.80, group size needed to eight. We included eight and 10 infants in each group. Differences between groups were determined using independent t tests or Mann-Whitney tests in case of normal or skewed distribution of the population, respectively. For differences in frequency of mode of delivery, χ2 test was used. A p value <0.05 was considered as statistically significant.
RESULTS
The stable isotope infusion was started either on day 1 (7 ± 4.8 h after birth, early group) or day 2 (31 ± 5.9 h after birth, late group). Clinical characteristics are displayed in Table 1. The maximum inspired oxygen fraction was significantly higher in the group of infants measured on day 2. Nutritional intakes before and during the study are shown in Table 2.
Concentrations of plasma precursor AAs.
Table 3 shows the plasma concentrations of all AAs involved in GSH synthesis with reference values obtained from healthy term breast-fed infants (19). Cystine concentration in the late group was significantly lower than in the early group and was below the reference value (19). Concentrations of glutamate, glutamine, methionine, and serine were not different between the groups, but glutamate concentrations were below reference values in both groups.
GSH concentrations and synthesis rates.
Free intraerythrocytic [1-13C]glycine enrichments reached a plateau after 4 h of infusion. Enrichments did not differ between the groups (mean 3.9 ± 0.9 and 3.4 ± 0.5 MPE in the early and late group, respectively, p = 0.18).
GSH kinetic data are shown in Figure 1. The concentration of erythrocyte GSH was significantly higher in the late group. However, FSRGSH was not different between groups. In addition, the ASRGSH did not differ significantly between the groups (p = 0.054).
Plasma levels of AOPP.
Plasma AOPP levels are shown in Figure 2. No differences were found between groups for plasma concentration of AOPP. The mean plasma concentration of AOPP of both groups was 217 ± 108 μM, which is in agreement with earlier studies on AOPP levels in preterm infants and indicates the presence of oxidative stress compared with term infants (15,20,21).
DISCUSSION
In preterm infants, there is a rapid decline of GSH immediately after birth, possibly as a result of higher oxidative stress after birth. Recently, we demonstrated that early AA administration directly after birth leads to an increased GSH concentration on postnatal day 2 (13). In this study, preterm infants receiving AAs from birth onward showed an age-related rise in GSH concentration without a concomitant rise in GSH synthesis rate, despite a higher inspired oxygen fraction in the late group.
The ASRGSH tended to be higher in the infants studied on day 2 (p = 0.054) with a difference of 2.5 mg/(kg · d) but was not significant between groups. Power calculation based on ASRGSH showed that at least four infants in each group should have been included to reach a physiologic difference of 4.5 mg/(kg · d). In this study, eight and 10 infants were included and therefore, this study has enough power. When speculating on a potential difference in ASR with an equal FSR, the observed difference in ASR would probably be almost exclusively attributed to the difference in concentration.
Because no differences were found in GSH synthesis rates, it would seem that the increased GSH concentration accompanying early AA administration is not caused by increased synthesis, suggesting that GSH consumption decreases upon AA administration.
Intracellular GSH concentration is determined by de novo synthesis; recycling of GSSG (oxidized, dimeric form of GSH) back to GSH; transport to the extracellular space; and utilization by peroxides, transferases, transhydrogenases, and transpeptidases (22). The method for measuring GSH concentration in this study does not discriminate between reduced and oxidized GSH. Therefore, the increased total GSH concentration in the late group cannot be explained by different recycling rates between the groups. Moreover, recycling of oxidized GSSG back to GSH seems to be enhanced rather than decreased in preterm infants (23,24). Consequently, the increased GSH concentration is likely to be caused by decreased consumption of GSH after early AA administration in preterm infants.
There are several possible explanations for this decreased GSH consumption upon AA administration. First, AAs can serve as antioxidants themselves. A study in healthy elderly people demonstrated reduced oxidative stress after the administration of essential AAs, including methionine and cysteine (both sulfur AAs) (25). It is possible that the latter two AAs were responsible for the antioxidant effect. Previous studies indeed showed that methionine residues may protect proteins from critical oxidative damage (26), and that oral supplements with whey proteins, which contain high amounts of sulfur AAs, increase plasma GSH levels in patients with HIV (27). The mechanism behind this increase in plasma GSH remains to be elucidated, because kinetic studies were not performed. Another possible explanation is that increased availability of AAs, as shown by increased plasma concentrations (13), up-regulates synthesis of other antioxidants. van den Akker et al. (28) showed that AA administration to preterm infants results in increased albumin synthesis and albumin also exerts antioxidant properties (29). Increased levels of other antioxidants might decrease the consumption of GSH, resulting in its increased concentrations and availability.
Besides antioxidant properties, GSH also functions as a cysteine reservoir. Consequently, GSH is broken down in response to shortage of cysteine and compromised protein synthesis. This follows from the observation that GSH levels become depleted if intakes of sulfur amino acids are minimal but sufficient to maintain protein synthesis at adequate levels (30,31). It is therefore possible that increased availability of cysteine reduces breakdown of GSH to generate free cysteine. Besides increased GSH concentration, plasma cysteine concentrations were also increased in infants receiving AAs from birth onward (13), suggesting decreased necessity for GSH breakdown to release cysteine. In this study, however, plasma cysteine (measured as cystine) concentrations dropped in the first day after birth resulting in lower plasma cysteine concentrations in the late group, whereas erythrocytic glutathione concentrations had increased. Although plasma and erythrocytes represent two compartments, this decrease suggests that serving as a substrate for GSH synthesis is the metabolic fate of cysteine, most likely due to increased requirements imposed by extrauterine life. However, it is recently demonstrated that a further increase in cyteine intake did not result in an increased GSH synthesis (32). Alternatively, cysteine might be used for synthesis of important proteins such as albumin.
AOPP concentrations typically increase significantly in the first week in preterm infants, both in hypoxic and nonhypoxic infants (20). In this study, however, plasma AOPP concentrations were not yet increased in the late group, even though the maximum inspired oxygen fraction was significantly higher in this group. It might well be that antioxidant defense mechanisms, such as the increased availability of GSH on day 2, avert some of the oxidative stress in preterm infants after birth.
There are some limitations in this study. First, it would have been useful to quantify oxidative stress in a broader perspective, going beyond protein oxidation only. For example, determining isoprostanes as a marker for lipid peroxidation (33). Furthermore, the ratio between erythrocytic reduced and oxidized GSH is also suggested to be an excellent marker for oxidative stress and is already used to this aim in infants (34). Regrettably, we could not obtain enough plasma for determining these markers, as a consequence of limited possibilities of blood withdrawal in these preterm infants. Second, the proportion of cesarean sections in the early group was significantly higher than that in the late group. It is argued that the mode of delivery might influence the degree of oxidative stress in the neonate, but literature on this topic is contradictory. Some authors report increased oxidative stress, whereas others report diminished oxidative stress (35–38).
At first glance, it can be said that the ranges of the FSR appear wide. The ranges are not caused by outliers but are caused by variation of glutathione FSR within the population. Although the range of fractional synthesis rates is between 30 and 70%/d, the SD is low in both groups compared with similar studies conducted by others (8,39,40).
In this study, we demonstrate an increase of GSH concentration in the first days after birth in preterm infants receiving AAs, without a concomitant rise in GSH synthesis. Normally, glutathione is rapidly depleted after birth in preterm infants, possibly as a consequence of increased oxidative stress postnatally. Whether AA could serve as antioxidants themselves, promote synthesis of other antioxidants, and thereby reduce the need for glutathione as an antioxidant, or whether the increased plasma cystine concentrations (13) decrease GSH breakdown to release free cysteine remains to be clarified.
Abbreviations
- AA:
-
amino acid
- AOPP:
-
advanced oxidized protein products
- ASR:
-
absolute synthesis rate
- FSR:
-
fractional synthesis rate
- GSH:
-
glutathione
- ROS:
-
reactive oxygen species
References
Richmond S, Goldsmith JP 2006 Air or 100% oxygen in neonatal resuscitation?. Clin Perinatol 33: 11–27
Nemeth I, Boda D 2001 Xanthine oxidase activity and blood glutathione redox ratio in infants and children with septic shock syndrome. Intensive Care Med 27: 216–221
Shoji H, Koletzko B 2007 Oxidative stress and antioxidant protection in the perinatal period. Curr Opin Clin Nutr Metab Care 10: 324–328
Friel JK, Friesen RW, Harding SV, Roberts LJ 2004 Evidence of oxidative stress in full-term healthy infants. Pediatr Res 56: 878–882
Munoz-Hoyos A, Bonillo-Perales A, Avila-Villegas R, Gonzalez-Ripoll M, Uberos J, Florido-Navio J, Molina-Carballo A 2007 Melatonin levels during the first week of life and their relation with the antioxidant response in the perinatal period. Neonatology 92: 209–216
Saugstad OD 1989 The oxygen radical disease in neonatology. Indian J Pediatr 56: 585–593
Saugstad OD 1999 The oxygen radical disease in neonatology. Semin Neonatol 3: 229–238
Darmaun D, Smith SD, Sweeten S, Sager BK, Welch S, Mauras N 2005 Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes. Diabetes 54: 190–196
Ahola T, Levonen AL, Fellman V, Lapatto R 2004 Thiol metabolism in preterm infants during the first week of life. Scand J Clin Lab Invest 64: 649–658
Giustarini D, Milzani A, Dalle-Donne I, Rossi R 2007 Red blood cells as a physiological source of glutathione for extracellular fluids. Blood Cells Mol Dis 40: 174–179
Jain A, Mehta T, Auld PA, Rodrigues J, Ward RF, Schwartz MK, Martensson J 1995 Glutathione metabolism in newborns: evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures. Pediatr Pulmonol 20: 160–166
Jean-Baptiste D, Rudolph N 2003 Sequential postnatal changes in erythrocyte glutathione and sulfhydryl content: a possible adaptational response to the extrauterine environment. Biol Neonate 84: 142–146
Te Braake FW, Schierbeek H, de Groof K, Vermes A, Longini M, Buonocore G, van Goudoever JB 2008 Glutathione synthesis rates after amino acid administration directly after birth in preterm infants. Am J Clin Nutr 88: 333–339
Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B 1996 Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49: 1304–1313
Buonocore G, Perrone S, Longini M, Terzuoli L, Bracci R 2000 Total hydroperoxide and advanced oxidation protein products in preterm hypoxic babies. Pediatr Res 47: 221–224
Laborie S, Lavoie JC, Pineault M, Chessex P 2000 Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions. Ann Pharmacother 34: 440–445
1993 The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. The International Neonatal Network. Lancet 342: 193–198
Schierbeek H, Te Braake F, Godin JP, Fay LB, van Goudoever JB 2007 Novel method for measurement of glutathione kinetics in neonates using liquid chromatography coupled to isotope ratio mass spectrometry. Rapid Commun Mass Spectrom 21: 2805–2812
Wu PY, Edwards N, Storm MC 1986 Plasma amino acid pattern in normal term breast-fed infants. J Pediatr 109: 347–349
Buonocore G, Perrone S, Longini M, Vezzosi P, Marzocchi B, Paffetti P, Bracci R 2002 Oxidative stress in preterm neonates at birth and on the seventh day of life. Pediatr Res 52: 46–49
Dani C, Giannini L, Bertini G, Pratesi S, Corsini I, Longini M, Buonocore G, Masini E, Rubaltelli FF 2007 Changes of nitric oxide, carbon monoxide and oxidative stress in term infants at birth. Free Radic Res 41: 1358–1363
Valencia E, Marin A, Hardy G 2001 Glutathione—nutritional and pharmacological viewpoints: part II. Nutrition 17: 485–486
Clahsen PC, Moison RM, Holtzer CA, Berger HM 1992 Recycling of glutathione during oxidative stress in erythrocytes of the newborn. Pediatr Res 32: 399–402
Frosali S, Di Simplicio P, Perrone S, Di Giuseppe D, Longini M, Tanganelli D, Buonocore G 2004 Glutathione recycling and antioxidant enzyme activities in erythrocytes of term and preterm newborns at birth. Biol Neonate 85: 188–194
Manzella D, Grella R, Esposito K, Cacciapuoti F, Arciello A, Giugliano D, Paolisso G 2005 Oral amino acid administration decreases oxidative stress and improves brachial reactivity in elderly individuals. Am J Hypertens 18: 858–863
Levine RL, Berlett BS, Moskovitz J, Mosoni L, Stadtman ER 1999 Methionine residues may protect proteins from critical oxidative damage. Mech Ageing Dev 107: 323–332
Micke P, Beeh KM, Schlaak JF, Buhl R 2001 Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest 31: 171–178
van den Akker CH, te Braake FW, Schierbeek H, Rietveld T, Wattimena DJ, Bunt JE, van Goudoever JB 2007 Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life. Am J Clin Nutr 86: 1003–1008
Halliwell B 1988 Albumin—an important extracellular antioxidant?. Biochem Pharmacol 37: 569–571
Stipanuk MH, Coloso RM, Garcia RA, Banks MF 1992 Cysteine concentration regulates cysteine metabolism to glutathione, sulfate and taurine in rat hepatocytes. J Nutr 122: 420–427
Stipanuk MH, Dominy JE Jr, Lee JI, Coloso RM 2006 Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J Nutr 136: 1652S–1659S
Te Braake FW, Schierbeek H, Vermes A, Huijmans JG, van Goudoever JB 2009 High-dose cysteine administration does not increase synthesis of the antioxidant glutathione preterm infants. Pediatrics 124: e978–e984
Roberts LJ, Morrow JD 2000 Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28: 505–513
Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Minana JB, Vina J 2002 Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants. Semin Perinatol 26: 406–410
Rogers MS, Mongelli JM, Tsang KH, Wang CC, Law KP 1998 Lipid peroxidation in cord blood at birth: the effect of labour. Br J Obstet Gynaecol 105: 739–744
Paamoni-Keren O, Silberstein T, Burg A, Raz I, Mazor M, Saphier O 2007 Oxidative stress as determined by glutathione (GSH) concentrations in venous cord blood in elective cesarean delivery versus uncomplicated vaginal delivery. Arch Gynecol Obstet 276: 43–46
Raijmakers MT, Roes EM, Steegers EA, van der Wildt B, Peters WH 2003 Umbilical glutathione levels are higher after vaginal birth than after cesarean section. J Perinat Med 31: 520–522
Inanc F, Kilinc M, Kiran G, Guven A, Kurutas EB, Cikim IG, Akyol O 2005 Relationship between oxidative stress in cord blood and route of delivery. Fetal Diagn Ther 20: 450–453
Badaloo A, Reid M, Forrester T, Heird WC, Jahoor F 2002 Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Am J Clin Nutr 76: 646–652
Lyons J, Rauh-Pfeiffer A, Ming-Yu Y, Lu XM, Zurakowski D, Curley M, Collier S, Duggan C, Nurko S, Thompson J, Ajami A, Borgonha S, Young VR, Castillo L 2001 Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Crit Care Med 29: 870–877
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Rook, D., te Braake, F., Schierbeek, H. et al. Glutathione Synthesis Rates in Early Postnatal Life. Pediatr Res 67, 407–411 (2010). https://doi.org/10.1203/PDR.0b013e3181d22cf6
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DOI: https://doi.org/10.1203/PDR.0b013e3181d22cf6
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