Papers by Waldemar Turski
Medycyna Ogólna i Nauki o Zdrowiu, Jun 30, 2011
Pestycydy to substancje syntetyczne lub naturalne stosowane do zwalczania organizmów szkodliwych ... more Pestycydy to substancje syntetyczne lub naturalne stosowane do zwalczania organizmów szkodliwych lub niepożądanych. Wśród obecnie stosowanych insektycydów najbardziej niebezpieczne, ze względu na ryzyko ostrych zatruć, są związki fosforoorganiczne. Jednak także długotrwała ekspozycja na toksyczne działanie pestycydów w najbliższym otoczeniu lub środowisku pracy niesie ze sobą ryzyko zdrowotne. Stopień narażenia środowiskowego i zawodowego na działanie insektycydów fosfoorganicznych może być monitorowany za pomocą biologicznych wskaźników oceniających ekspozycję, ryzyko zdrowotne czy osobniczą wrażliwość na toksyczne działanie tych pestycydów. Praca przedstawia najczęściej stosowane biomarkery wczesnych skutków biologicznych ekspozycji na pestycydy fosfoorganiczne, ze szczególnym naciskiem na genotoksyczne skutki powodowane narażeniem na te związki. Podsumowuje również możliwości i ograniczenia, jakie posiadają biomarkery wykorzystywane do oceny i identyfi kacji ekspozycji środowiskowej/zawodowej na działanie pestycydów.
Neurochemical Research, Jul 21, 2016
oligodendrocytes. This study contributes to the elucidation of effects of KYNA on oligodendrocyte... more oligodendrocytes. This study contributes to the elucidation of effects of KYNA on oligodendrocytes in vitro, yet further analyses are necessary to explain the mechanisms behind the damage and loss of myelin sheaths.
Research Square (Research Square), Apr 26, 2023
Kynurenic acid (KYNA) is a bioactive compound exhibiting positive effects on human health due to ... more Kynurenic acid (KYNA) is a bioactive compound exhibiting positive effects on human health due to its antioxidant, anti-in ammatory and anti-virus properties. Despite notable progress in the research focused on KYNA observed during the last 10 years, KYNA presence in ax (Linum usitatissimum L.) has not been proven so far. In the present study, parts of ax plants were analysed for KYNA synthesis. Moreover, eight different cultivars of ax seeds were tested for KYNA presence, resulting in maximally 0.432 µg/g FW in the seeds of the cultivar Jan. The level of KYNA was also tested in stems and roots of two selected ax cultivars: an oily cultivar (Linola) and a brous cultivar (Nike). The exposure of plants to the KYNA precursors tryptophan and kynurenine resulted in higher KYNA accumulation in ax shoots and roots. Thus, the obtained results indicate that KYNA might be synthesized in ax. The highest amount of KYNA (295.9 µg/g dry weight [DW]) was detected in ax roots derived from plants grown in tissue cultures supplemented with 10 mM tryptophan. The content of KYNA in ax cultivated on tryptophan-enriched medium was about 90-fold higher than in potato tubers and 600-fold higher than in ax seeds in the present study. These data suggest that ax tissue cultures enriched with tryptophan might be an e cient source of KYNA.
Scientific Reports, Aug 2, 2023
Tryptophan breakdown metabolites formed along the kynurenine pathway play a significant role in p... more Tryptophan breakdown metabolites formed along the kynurenine pathway play a significant role in pregnancy and fetal development. To understand their involvement, it is crucial to quantify the levels of tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA) in relevant biological samples such as the placenta, fetal membranes, and umbilical cord. This study used liquid chromatographytandem mass spectrometry (LC-MS/MS) to determine TRP, KYN, and KYNA levels. The LC-MS/MS method was optimized for high sensitivity and specificity, demonstrating good reproducibility with a precision of < 10% CV and an accuracy of 85-115%. The lower limit of quantification for both TRP and KYN was 0.5 µg/ml, while for KYNA, it was 0.5 ng/mL. The method exhibited linearity within the examined range of concentrations in the homogenate, ranging from 0.5 to 30 µg/ml for TRP and KYN and from 0.5 to 25 ng/ml for KYNA. Using this method, we found significant differences in the concentrations of these substances in investigated maternal-fetal compartments. Placenta samples exhibited higher KYN and lower KYNA concentrations than the umbilical cord and fetal membrane, indicating a potentially important role for kynurenines in late pregnancy. Collectively, this finding may facilitate further research and provide inside into the involvement of the kynurenine pathway of TRP metabolism in fetal development. Abbreviations AhR Aryl hydrocarbon receptor ANOVA Analysis of variance CV Coefficient variation dMRM Dynamic multiple reaction monitoring ESI Electrospray ionization GPR35 G-protein coupled receptor 35 GPR139 G-protein coupled receptor 127 GPR142 G-protein coupled receptor 142 IDO Indoleamine 2,3-dioxygenase KAT Kynurenine aminotransferase KP Kynurenine pathway KYN Kynurenine KYNA Kynurenic acid
Pharmacological Research, May 1, 1998
Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the aim of this study ... more Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the aim of this study was to examine possible interactions between non-steroidal anti-inflammatory drugs and two conventional antiepileptic drugs in terms of their anticonvulsive activity and side-effects. Also, the plasma levels of antiepileptics were measured in order to delineate possible pharmacokinetic interactions. The following non-steroidal anti-inflammatory drugs (NSAIDs) were studied: acetylsalicylic
Neuroscience Letters, Feb 1, 1985
Antagonists of neuronal excitation induced by dicarboxylic amino acids were tested in genetically... more Antagonists of neuronal excitation induced by dicarboxylic amino acids were tested in genetically spastic rats of the Han-Wistar strain. These animals exhibit an increased muscle tone which can be measured as a spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Compounds that block excitation due to N-methyl-D-aspartic acid reduced the spontaneous activity measured in the electromyogram in a dose-related manner. The most potent compounds, 2-amino-7phosphonoheptanoic and kynurenic acids were effective muscle relaxants when given either intraperitoneally or intracerebroventricularly. 2-Amino-5-phosphonopentanoic acid possessed much weaker muscle relaxant activity, while L-glutamic acid diethylester was inactive by either route. The results suggest that blockade of N-methyl-D-aspartic acid receptors results in a myorelaxant effect. Specific antagonists of excitation at N-methyl-D-aspartic acid receptors may provide a new class of muscle relaxants. The dicarboxylic amino acids, aspartic and glutamic acids, appear to act as excitatory neurotransmitters throughout the central nervous system in mammals [12]. Since the regulation of muscle tone depends on the equilibrium between excitatory and inhibitory neurotransmission within the spinal cord and supraspinal motor centers, one may assume that a pathologically increased muscle tone can be ameliorated by antagonists of excitatory amino acids. Neuronal excitation produced by dicarboxylic amino acids is antagonized by w-phosphonic et-amino carboxylic acids and certain L-tryptophan metabolites [6, 14]. The phosphonic amino acids, 2-amino-5-phosphonopentanoate (2-APP) and 2-amino-7-phosphonoheptanoate (2-APH), have been reported to antagonize N-methyl-D-aspartic acid (NMDA)induced responses, but not glutamate and kainate responses in both cat and frog spinal neurons [6, 8]. More recent studies have demonstrated antagonism by 2-APP
Medycyna Ogólna i Nauki o Zdrowiu, Jun 30, 2011
Pestycydy to substancje syntetyczne lub naturalne stosowane do zwalczania organizmów szkodliwych ... more Pestycydy to substancje syntetyczne lub naturalne stosowane do zwalczania organizmów szkodliwych lub niepożądanych. Wśród obecnie stosowanych insektycydów najbardziej niebezpieczne, ze względu na ryzyko ostrych zatruć, są związki fosforoorganiczne. Jednak także długotrwała ekspozycja na toksyczne działanie pestycydów w najbliższym otoczeniu lub środowisku pracy niesie ze sobą ryzyko zdrowotne. Stopień narażenia środowiskowego i zawodowego na działanie insektycydów fosfoorganicznych może być monitorowany za pomocą biologicznych wskaźników oceniających ekspozycję, ryzyko zdrowotne czy osobniczą wrażliwość na toksyczne działanie tych pestycydów. Praca przedstawia najczęściej stosowane biomarkery wczesnych skutków biologicznych ekspozycji na pestycydy fosfoorganiczne, ze szczególnym naciskiem na genotoksyczne skutki powodowane narażeniem na te związki. Podsumowuje również możliwości i ograniczenia, jakie posiadają biomarkery wykorzystywane do oceny i identyfi kacji ekspozycji środowiskowej/zawodowej na działanie pestycydów.
Journal of Chromatographic Science, Oct 27, 2020
This paper is a continuation of lipophilicity research on 14 compounds (tryptophan, kynurenine pa... more This paper is a continuation of lipophilicity research on 14 compounds (tryptophan, kynurenine pathway products, auxin pathway products, serotonin pathway products, tryptamine, as well as two synthetic auxin analogs): indole-2-acetic acid sodium salt (IAA), serotonin, 5-hydroxy-Ltryptophan, tryptamine, L-tryptophan, L-kynurenine (KYN), kynurenic acid (KYA), 3-hydroxy-DLkynurenine, naphtyl-1-acetamide, indole-3-propionic acid (IPA), naphthalene-1-acetic acid (NAA), indole-3-butyric acid (IBA), indole-3-pyruvic acid (IPV), as well as melatonin. They were chromatographed in high performance liquid chromatography gradient conditions on tree stationary phases (C18, CN, DIOL) using three modifiers on each phase (methanol, acetonitrile and acetone). The resulting retention data was correlated with computational lipophilicity indices. Six compounds were proven to be ionized in neutral pH physiological conditions (IAA, KYA, IPA, NAA, IBA and IPV) and they were rechromatographed with acidic mobile phase to enhance the resulting dataset. It can be concluded that the retention times are highly correlated with lipophilicity regardless of used modifier and column and the main differentiating trend can be only connected to presence of naphthalene or indole ring. The principal component analysis, additive linear modeling, as well as multiplicative trilinear parallel factor analysis (PARAFAC) modeling helped to understand the internal structure of the obtained results.
Restorative Neurology and Neuroscience, Sep 24, 2020
Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, ... more Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a "Systemic AhR Activation Syndrome" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D 3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.
Pharmacological Reports, Sep 1, 2010
Pharmacological Reports, Mar 1, 2011
Kynurenic acid (KYNA) is an endogenous brain constituent that inhibits the activity of all three ... more Kynurenic acid (KYNA) is an endogenous brain constituent that inhibits the activity of all three ionotropic excitatory amino acid (EAA) receptors. Cerebral synthesis of KYNA from its bioprecursor L-kynurenine is catalyzed by aminotransferases (KAT I and KAT II) localized preferentially within astrocytes. The possible role of altered KYNA-mediated modulation of EAA receptors in the human neuropathology has been postulated. The disturbances of KYNA production have been linked to the occurrence of epilepsy. The anticonvulsant and neuroprotective role of KYNA in vivo and in vitro is well documented. In this study the influence of chemical convulsants: bicuculine and pentylenetetrazole on the brain production of KYNA was investigated. The experiments were performed in vitro in rat cortical slices. Bicuculine at the concentration of 0.5, 1
Investigative Ophthalmology & Visual Science, May 1, 2005
Experimental Eye Research, Mar 1, 2022
Kynurenine aminotransferases (KAT) are enzymes catalyzing formation of kynurenic acid (KYNA) from... more Kynurenine aminotransferases (KAT) are enzymes catalyzing formation of kynurenic acid (KYNA) from kynurenine. KYNA is a Janus-faced molecule of high biological activity. On the one hand KYNA was identified as a UV filter and neuroprotectant with free radical scavenging properties, but on the other hand it may contribute to photodamage of lens proteins resulting in cataract formation. Fuchs endothelial corneal dystrophy (FECD) and keratoconus (KC) are common, vision threatening corneal dystrophies whose etiology is not fully understood. In our previous works, we confirmed the presence of KATs in the human cornea together with GPR35, a receptor for KYNA. This prompted us to investigate the potential changes in the expression of three isoforms: KAT I, KAT II, and KAT III in normal and FECD- and KC-affected corneas. Immunohistochemistry accompanied by gene expression data mining revealed that the levels of neither KAT I, KAT II, nor KAT III are affected in FECD and KC. This constitutes evidence against the involvement of KATs in the pathophysiology of FECD and KC.
Journal of Pharmaceutical and Biomedical Analysis, Nov 1, 2020
A rapid, reliable and sensitive liquid chromatography quadrupole time-of-flight mass spectrometry... more A rapid, reliable and sensitive liquid chromatography quadrupole time-of-flight mass spectrometry method for the determination of tryptophan and its metabolite kynurenine in milk formulas for neonates and infants was developed and validated. Two extraction techniques based on EMR Lipid QuEChERS and liquid-liquid extraction with diethyl ether to extract lipids and methanol to precipitate the protein were tested and compared. Four different infant formula products were randomly selected and evaluated for the effect of co-extracted matrix components on the quantitative analysis results. The influence of matrix components on analytical signals was normalized by the use of stable isotope-labeled standards and matrix-matched calibration. The developed method was found to be sensitive and effective for both analytes in all the examined infant formulas with satisfactory linearity (R 2 ≥ 0.9995), recovery in the range of 75.7% ± 4.5-99.0% ± 1.1, and intra-and inter-day precision with the coefficient of variation below 6.3% and 17.9%, respectively. The limits of detection (LOD) and quantification (LOQ) for both compounds differed significantly between the examined formulas. The LOD and LOQ values were found to be in the range of 2.18-9.85 g/g and 6.61-29.84 g/g for the determination of tryptophan and in the range of 0.21-2.71 g/g and 0.63-8.23 g/g for the determination of kynurenine, respectively. The method was proved to be suitable for the determination of tryptophan and kynurenine in infant formulas, and it can be used to study the link between tryptophan metabolism via kynurenine pathway and metabolic disorders in infants.
Experimental Eye Research, Feb 1, 2019
The presence and distribution of G protein-coupled receptor 35 (GPR35) in the human corneaevidenc... more The presence and distribution of G protein-coupled receptor 35 (GPR35) in the human corneaevidences from in silico gene expression analysis and immunodetection
Neuroscience Letters, Mar 1, 1985
2-chloroadenosin e-picro toxin-bicucull ine-Ro 15-1788-CGS 8216-{3-CCMaminoph ylline-electromyogr... more 2-chloroadenosin e-picro toxin-bicucull ine-Ro 15-1788-CGS 8216-{3-CCMaminoph ylline-electromyogram-rat T he role pla yed by ben zodi azepine (BDZ) receptor s and OAB Aergic mechan isms in the mu scle relaxa nt effect o f th e ade no sine recep tor a go nist , 2-chloroa denos ine (2-C LA) wa s evaluated in genetica lly spastic ra ts. 2-CLA reduc ed in a dose-related manner the spontaneous tonic activity in the electromyogram (EM G) o f the gastrocnemius-soleus muscle. Wh ile the m uscle rela xant ef fect produced by t he adenosine an alogue was a bolished by a minop hylline, a methylxanthi ne with poten t anta gonistic a ctivity o f aden osine-med iat ed inhibition , the two i-amin obut yric acid (OABA) antagonists bicuculline a nd picrot oxin did not r everse it. Neit her Ro 15-1788 nor COS 8216, specific BDZ receptor antagonists, nor {j-ca rboline-3-car boxyJic aci d methyl ester, an inverse agonist at BDZ receptors, affected the depressant effect of2-CLA in the EMO. These results suggest that 2-C LA doe s not intera ct with OABA or SDZ recepto r-mediated events in vivo to produce the muscle relaxa nt actio n. It is proposed tha t pu rinergi c mechanisms ma y be invo lved in the muscle relaxa nt ef fects of a vari ety of drugs.
PubMed, Sep 25, 2003
The accumulated data indicate that massively released excitatory amino acids play a major role in... more The accumulated data indicate that massively released excitatory amino acids play a major role in mediating the acute ischemic neuronal degeneration. Kynurenic acid (KYNA), the endogenous glutamate receptor antagonist, displaying a particularly high affinity for the glycine-site of N-methyl-D-aspartate (NMDA) receptor, was shown to ameliorate ischemic brain damage and its altered metabolism was implicated in the pathogenesis of neurodegeneration during ischemia/anoxia. Thus, we investigated the effect of transient global ischemia in gerbils on the endogenous levels of KYNA and the activity of its biosynthethic enzymes, kynurenine aminotransferases I (KAT I) and II (KAT II) in the hippocampus, 24 and 72 h after the ischemic episode. The level of KYNA in CA1 area was not altered 24 and 72 h following transient global ischemia (39.7 +/- 3.1 vs. 44.8 +/- 4.2, and 46.3 +/- 4.0 vs. 47.8 +/- 3.9 fmol/mg of tissue). Similarly, the activities of KATs in CA1 area were not changed and reached 1.91 +/- 0.11 vs. 1.8 +/- 0.19 and 1.86 +/- 0.1 vs. 1.7 +/- 0.15 (KAT I), and 0.56 +/- 0.2 vs. 0.43 +/- 0.16 and 0.54 +/- 0.08 vs. 0.55 +/- 0.17 (KAT II) pmol KYNA/mg of tissue/h, respectively. The presented data indicate that KYNA production is preserved in CA1 area of gerbil hippocampus during early stages after ischemic insult.
European Journal of Pharmacology, Apr 1, 1987
The effect of T-D-glutamylaminomethylsulphonate (T-D-GAMS) and 1-(p-bromobenzoyl)-piperazine-2,3-... more The effect of T-D-glutamylaminomethylsulphonate (T-D-GAMS) and 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylate (pBB-PzDA) on convulsions elicited by intracerebroventricular application of kainate (KA) and Nmethyl-D-aspartate (NMDA) was studied in mice. T-D-GAMS, 0.0025-1.0 /~mol, and pBB-PzDA, 0.001-0.2 /tmol, were preferentially active against myoclonic seizures induced by kainate, but had also pronounced anticonvulsant action against NMDA. Although pBB-PzDA was a more potent anticonvulsant relative to T-D-GAMS, T-D-GAMS displayed higher kainate-selectivity. T-D-GAMS, 0.025 and 0.5 /~mol, and pBB-PzDA, 0.1 #tool, blocked myoclonic seizures induced by kainate in the presence of 2-amino-7-phosphonoheptanoate, a selective antagonist at the NMDA receptor, with potency comparable to that for antagonism of seizures produced by kainate alone. These results indicate that antagonism at kainate receptors may contribute to anticonvulsant drug action. T-D-Glutamylaminomethylsulphonic acid; 1-(p-Bromobenzoyl)-piperazine-2,3-dicarboxylic acid; Excitatory amino acid antagonists; Seizures; (Mouse)
Investigative Ophthalmology & Visual Science, 2003
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Papers by Waldemar Turski