Dissociation of neopterin and 7,8-dihydroneopterin from plasma components before HPLC analysis

Flavall, Elizabeth A.; Crone, Elizabeth M.; Moore, Grant A.; Gieseg, Steven P.

doi:10.1016/j.jchromb.2007.12.019

Cited by 37 publications

(27 citation statements)

References 26 publications

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“…Most probably, this discrepancy depends on the precipitation method applied for serum protein separation. When acidic milieu is used, partial oxidation may occur, which contributes to higher neopterin levels due to oxidation of 7,8-dihydroneopterin to neopterin [26]. Only separation of unwanted serum protein with molecular sieves or precipitation with acetonitrile (CH 3 CN) could be employed as alternative techniques that are not associated with 7,8-dihydroneopterin oxidation.…”

Section: Discussionmentioning

confidence: 99%

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Geisler

Mayersbach²,

Becker

et al. 2015

Pteridines

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AbstractFormation of neopterin, a biomarker of the activated human immune system, is linked with tryptophan (TRP) and phenylalanine (PHE) metabolism. To obtain normal values, in this study, serum concentrations of neopterin as well as of TRP, PHE and their respective metabolites kynurenine (KYN) and tyrosine (TYR) were investigated in 100 successive blood donor serum specimens from the University Clinics of Innsbruck, Austria. In addition, nitrite concentrations were determined. Donors had passed anamnestic examination at entry and were therefore considered as healthy. The mean age of participants was 49±11.4 (mean±SD) years; 18% were older than 60 years. Both genders were included in the analysis. Neopterin concentrations measured by enzyme-linked immunosorbent assay were 5.9±1.6 nmol/L (mean±SD). Levels of amino acids and metabolites were determined by HPLC. Mean KYN and TRP concentrations were 1.78±0.42 μmol/L and 67.4±10.2 μmol/L, respectively. KYN to TRP ratio (KYN/TRP), an estimate for the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase, was 26.7±6.2 μmol/mmol. Mean PHE and TYR concentrations were 65.2±11.1 μmol/L and 90.6±22.9 μmol/L. PHE to TYR ratio (PHE/TYR), an estimate for the activity of PHE-converting enzyme phenylalanine hydroxylase, was 0.75±0.14 μmol/μmol. Nitrite concentrations, estimated by Griess-Ilosvay reagent, were 44.9±32.0 μmol/L. Males were taller and heavier than females (both p<0.01), but body mass index did not differ. Males presented with significantly higher TRP and TYR concentrations than females (both p<0.05). There existed significant correlations between neopterin and KYN (rs=0.368), KYN/TRP (rs=0.453), TYR (rs=–0.267; all p<0.01) and PHE/TYR (rs=0.236; p<0.05) concentrations. Data indicate that also in a population of healthy individuals an association exists between “low-grade” immune activation as is indicated by slightly higher neopterin concentrations and biochemical alterations in the amino acid metabolism. Although minor, such changes may interfere with psychoneuroimmunological regulatory networks and thus be of clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Geisler

Mayersbach²,

Becker

et al. 2015

Pteridines

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“…The increase in NP concentrations observed postoperatively in the on-pump group could represent a cumulative consequence of blood being in contact with the tubing associated with the CPB equipment and subsequent activation of monocytes/macrophages [16,25] . Measurements of NP in serum by HPLC is flawed by the fact that the reduced NP derivative, 7.8-dyhydroneopterin, undergoes oxidation to NP in acidic solution and the presence of air oxygen [13,26] . This fact may explain why the urine NP concentrations are in accord with data in the literature [27] (in this case no acidification is necessary/performed), whereas the serum concentrations are approximately twice as high compared with literature data on the basis of immunoassays.…”

Section: Discussionmentioning

confidence: 99%

Role of Neopterin, C-Reactive Protein and Myeloperoxidase in Patients Undergoing Cardiopulmonary Bypass

Ayaz¹,

Ünlü

Sucu³

et al. 2010

Med Princ Pract

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Objective: The aim of the present study was to investigate the role of neopterin (NP), C-reactive protein (CRP) and myeloperoxidase (MPO) in patients undergoing coronary artery bypass grafting with or without cardiopulmonary bypass (CPB). Patients and Methods: Forty patients submitted for elective coronary artery bypass grafting were included in this prospective study. Patients were divided into two groups of 20 individuals, those who did not undergo CPB (group 1), aged 54.1 ± 13.5 years, and those who did (group 2), aged 60.2 ± 11.7 years. In group 1, there were 17 males and 3 females, while in group 2, there were 16 males and 4 females. Serum CRP, serum and urine NP and leukocyte MPO activity were measured preoperatively, at the end of surgery, and 4, 24 and 72 h after surgery using high-performance liquid chromatography, immunoturbidimetry and the reduction in o-dianizidine, respectively. Results: The level of serum NP was higher preoperatively and at the end of surgery (0 h), 4, 24, and 72 h after the operation in those who underwent CPB compared to those who did not. However, there was no significant difference in NP concentrations between the two groups at any time except 24 h after surgery (p = 0.002). Urine NP concentrations showed similar values preoperatively but increased postoperatively in both groups of patients. The only significant difference in urine NP concentration between the two groups occurred at 0 and 24 h after surgery (p = 0.001, p = 0.000). Serum CRP concentrations showed similar values preoperatively, at the end of surgery and 72 h after the operation and increased at 4 and 24 h postoperatively in both groups. The only significant difference in CRP concentration between the two groups occurred 4 and 24 h after surgery (p = 0.024 and p = 0.000, respectively). MPO levels were found to be increased in the CPB patients when compared to those patients who did not undergo CPB. However, the difference between the groups was not statistically significant. Conclusion: Our data show that CPB induced a rise in NP and CRP levels.

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“…Neopterin and total neopterin (neopterin plus 7,8-dihydroneopterin) were measured by reverse-phase HPLC analysis with fluorescence detection as previously described [28]. During the study, improvements in HPLC analysis from plaque number 19 onwards allowed measurement of both neopterin and the unoxidised form of 7,8-dihydroneopterin.…”

Section: Methodsmentioning

confidence: 99%

“…7,8-Dihydroneopterin measurement at the levels found within plasma and tissues ( < 50 nmol/L) requires oxidation of 7,8-dihydroneopterin to the highly fluorescent neopterin. The amount of neopterin measured after iodide oxidation is traditionally expressed as total neopterin as it is a measure of the neopterin plus 7,8-dihydroneopterin oxidised to neopterin [28].…”

Section: Methodsmentioning

confidence: 99%

Neopterin and 7,8-dihydroneopterin are generated within atherosclerotic plaques

et al. 2015

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AbstractPlasma neopterin correlates with the level of cardiovascular disease. Neopterin is the oxidation product of 7,8-dihydroneopterin, which is released by γ-interferon-stimulated macrophages. 7,8-Dihydroneopterin is a potent antioxidant, which inhibits lipid oxidation, macrophage cell death and scavenger receptor CD36 expression. The concentration of neopterin within atherosclerotic plaques was measured in tissue removed from carotid and femoral arteries. The excised plaques were cut into 3-mm-thick sections, and each section was analysed for neopterin, total neopterin, cholesterol, lipid peroxides, α-tocopherol and protein-bound 3,4-dihydroxyphenylalanine. Selected plaques were placed in tissue culture, and the media was analysed for 7,8-dihydroneopterin and neopterin release. Total neopterin levels ranged from 14 to 18.8 nmol/g of tissue. Large ranges of values were seen both within the same plaque and between plaques. No correlation between neopterin and any of the other analytes was observed, nor was there any significant trend in levels along the length of the plaques. γ-Interferon stimulation of cultured plaque generated total neopterin concentrations from 1 to 4 nmol/(g 24 h). The level of 7,8-dihydroneopterin generated within the plaque was within the range that inhibits lipid oxidation. The data show that atherosclerotic plaques are extremely dynamic in biochemistry and are the likely source of the plasma 7,8-dihydroneopterin and neopterin.

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Dissociation of neopterin and 7,8-dihydroneopterin from plasma components before HPLC analysis

Cited by 37 publications

References 26 publications

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Role of Neopterin, C-Reactive Protein and Myeloperoxidase in Patients Undergoing Cardiopulmonary Bypass

Neopterin and 7,8-dihydroneopterin are generated within atherosclerotic plaques

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