Fast and Sensitive HPLC Method for The Determination of Neopterin, Kynurenine and Tryptophan in Amniotic Fluid, Malignant Effusions and Wound Exudates

Krcmova, Lenka Kujovska; Červinková, Barbora; Solichová, Dagmar; Sobótka, L.; Hansmanova, Lenka; Melichar, Bohuslav; Solich, Petr

doi:10.4155/bio.15.175

Cited by 20 publications

(19 citation statements)

References 34 publications

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“…Moreover, IDO activity and Kyn have been linked to anti-fibrotic responses of dermal fibroblasts via formation of an aryl hydrocarbon receptor (AhR)kynurenine ligand complex which mediates increased expression of metalloproteinase 1 in the extracellular matrix (21). Kyn to Trp ratio (Kyn/Trp) has been suggested to be a direct measure of IDO activity (22). In addition, IDO gene polymorphisms in SSc have been correlated with impaired suppressive activity of patient CD8+ Treg cells (23).…”

Section: Introductionmentioning

confidence: 99%

Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis

Campochiaro

Lytton²,

Nihtyanova

et al. 2019

Clinical Immunology

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Systemic sclerosis (SSc) is a systemic disease characterized by vasculopathy, progressive fibrosis and autoimmune activation. Tryptophan (Trp) metabolism has been linked to altered immune cell function and to malignancy. We have investigated the role of Trp metabolic pathway in SSc measuring serum Trp, Kynurenine (Kyn) and Trp/Kyn ratio in a cohort of 97 SSc patients and 10 healthy controls. Association with disease characteristics was evaluated. We found that Trp levels in SSc patients were significantly lower compared to HCs. We also found that patients with diffuse cutaneous (dcSSc) had lower levels of Trp compared to limited cutaneous (lcSSc). These results were paralleled by higher levels of Kyn found in SSc patients compared to HCs and significantly lower levels in dcSSc compared to lcSSc. The autoantibody profile was also found to be significantly associated with Kyn and Trp levels as anti-RNA-polymerase III (ARA) positive patients were shown to have lower Trp levels and higher Kyn levels compared with anticentromere and anti-topoisomerase I positive patients. Moreover, the highest Trp/Kyn was found in ARA+ patients with dcSSc, suggesting that an activation of the Kyn pathway, is more specifically associated with this subset of SSc patients. Stability over time makes these markers of Trp metabolism feasible for SSc stratification.

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Section: Introductionmentioning

confidence: 99%

Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis

Campochiaro

Lytton²,

Nihtyanova

et al. 2019

Clinical Immunology

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“…LC has been often used for this purpose. There are methods employing various detection modalities: UV absorbance , fluorescence , electrochemical methods as well as MS . The LC separation is mostly achieved on octadecyl silica (ODS) columns.…”

Section: Chromatographic Analysis Of Tryptophan Metabolitesmentioning

confidence: 99%

“…The most popular method of ʟ‐kynurenine (ʟ‐Kyn) quantification is HPLC with UV detection . However, sensitivity and selectivity using HPLC‐based methods may be insufficient for determination of ʟ‐Kyn present at micromolar concentrations in biological fluids or tissues.…”

Section: Chromatographic Analysis Of Tryptophan Metabolitesmentioning

confidence: 99%

Chromatographic analysis of tryptophan metabolites

Sadok

Gamian

Staniszewska

2017

J of Separation Science

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The kynurenine pathway generates multiple tryptophan metabolites called collectively kynurenines and leads to formation of the enzyme cofactor nicotinamide adenine dinucleotide. The first step in this pathway is tryptophan degradation, initiated by the rate‐limiting enzymes indoleamine 2,3‐dioxygenase, or tryptophan 2,3‐dioxygenase, depending on the tissue. The balanced kynurenine metabolism, which has been a subject of multiple studies in last decades, plays an important role in several physiological and pathological conditions such as infections, autoimmunity, neurological disorders, cancer, cataracts, as well as pregnancy. Understanding the regulation of tryptophan depletion provide novel diagnostic and treatment opportunities, however it requires reliable methods for quantification of kynurenines in biological samples with complex composition (body fluids, tissues, or cells). Trace concentrations, interference of sample components, and instability of some tryptophan metabolites need to be addressed using analytical methods. The novel separation approaches and optimized extraction protocols help to overcome difficulties in analyzing kynurenines within the complex tissue material. Recent developments in chromatography coupled with mass spectrometry provide new opportunity for quantification of tryptophan and its degradation products in various biological samples. In this review, we present current accomplishments in the chromatographic methodologies proposed for detection of tryptophan metabolites and provide a guide for choosing the optimal approach.

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“…Initial levels of neopterin, tryptophan, kynurenine, and their ratios in serum and urine, were determined from venous blood samples and urine samples taken just prior to surgery. From the 1 st to the 6 th postoperative day, kynurenine and tryptophan levels, as well as their ratios in serum, urine, and drainage fluid, were monitored until the time of their removal [ 13 , 14 ]. Also on the 2 nd and 5 th postoperative days, leukocyte counts and CRP levels in venous blood were assessed.…”

Section: Methodsmentioning

confidence: 99%

Neopterin, kynurenine and tryptophan as new biomarkers for early detection of rectal anastomotic leakage.

Dušek

Örhalmi

Sotona

et al. 2018

Videosurgery and Other Miniinvasive Techniques

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IntroductionAt present, there are no strong predictors, nor a useful scoring system, that clearly identifies patients at risk for anastomotic leakage.AimThis study aimed to investigate a new method that assesses this risk by monitoring levels of neopterin, tryptophan, and kynurenine, in bodily fluids.Material and methodsThis prospective study included patients who underwent elective rectal resection for carcinoma. The basic condition for inclusion was rectal anastomosis using the double-stapling technique. Preoperative levels of neopterin, tryptophan, kynurenine, and their ratios, were assessed with blood and urine samples. These levels were then monitored for 6 postoperative days in venous blood, urine, and abdominal drainage fluid.ResultsA total of 42 patients were enrolled in the study. Thirty-six patients underwent a laparoscopic resection and 6 patients had an open procedure. No differences were found among neopterin, tryptophan, and kynurenine serum levels. However, the groups were observed to have significant differences in the urinary neopterin/creatinine ratio: the preoperative neopterin/creatinine ratio was 139.5 μmol/mol in the group with leakage, vs 114.8 μmol/mol in the group without complications, p = 0.037. The same results were observed during the postoperative period, p = 0.012. Additionally, the group with complications had a higher mean value of neopterin in drainage fluid, p = 0.048.ConclusionsOur study demonstrated that high preoperative levels of urinary neopterin could be interpreted as a risk for anastomotic leakage. Moreover, pathological levels of neopterin in urine and abdominal drainage fluid could be useful for early identification of anastomotic leakage during the postoperative period prior to its clinical development.

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Fast and Sensitive HPLC Method for The Determination of Neopterin, Kynurenine and Tryptophan in Amniotic Fluid, Malignant Effusions and Wound Exudates

Abstract: The method was applied to real clinical sample measurements, and it will be used to monitor neopterin, kynurenine and tryptophan levels in biological fluids to assess the patient response to therapy and clinical status.

Cited by 20 publications

References 34 publications

Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis

Elevated kynurenine levels in diffuse cutaneous and anti-RNA polymerase III positive systemic sclerosis

Chromatographic analysis of tryptophan metabolites

Neopterin, kynurenine and tryptophan as new biomarkers for early detection of rectal anastomotic leakage.

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