Wyniki wyszukiwania - Biblioteka Nauki

1

Conversion L-tryptophan to melatonin in the gastrointestinal tract: the new high performance liquid chromatography method enabling simultaneous determination of six metabolites of L-tryptophan by native fluorescence and UV-Vis detection

100%

Zagajewski J. , Drozdowicz D. , Brzozowska I. , Hubalewska-Mazgaj M. , Stelmaszynska T. , Laidler P. M. , Brzozowski T.

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2012

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tom 63

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nr 6

2

Peripheral distribution of kynurenine metabolites and activity of kynurenine pathway enzymes in renal failure

100%

Pawlak D. , Tankiewicz A. , Matys T. , Buczko W.

Journal of Physiology and Pharmacology

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2003

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tom 54

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nr 2

EN

We investigated L-kynurenine distribution and metabolism in rats with experimental chronic renal failure of various severity, induced by unilateral nephrectomy and partial removal of contralateral kidney cortex. In animals with renal insufficiency the plasma concentration and the content of L-tryptophan in homogenates of kidney, liver, lung, intestine and spleen were significantly decreased. These changes were accompanied by increase activity of liver tryptophan 2,3-dioxygenase, the rate-limiting enzyme of kynurenine pathway in rats, while indoleamine 2,3-dioxygenase activity was unchanged. Conversely, the plasma concentration and tissue content of L-kynurenine, 3-hydroxykynurenine, and anthranilic, kynurenic, xanthurenic and quinolinic acids in the kidney, liver, lung, intestine, spleen and muscles were increased. The accumulation of L-kynurenine and the products of its degradation was proportional to the severity of renal failure and correlated with the concentration of renal insufficiency marker, creatinine. Kynurenine aminotransferase, kynureninase and 3-hydroxyanthranilate-3,4-dioxygenase activity was diminished or unchanged, while the activity of kynurenine 3-hydroxylase was significantly increased. We conclude that chronic renal failure is associated with the accumulation of L-kynurenine metabolites, which may be involved in the pathogenesis of certain uremic syndromes.

3

Kynurenine and its metabolites in the rat with experimental renal insufficiency

100%

Pawlak D. , Tankiewicz A. , Buczko W.

Journal of Physiology and Pharmacology

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2001

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tom 52

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nr 4,2

EN

In uremia a great number of the endogenous metabolites that are ordinarily excreted in urine accumulate in the blood. Among these are the products of KYN degradation. In the present study we evaluated the peripheral KYN metabolism in the various stages of the rat experimental chronic renal insufficiency. Our results showed significant disturbances in peripheral kynurenic pathway, which resulted in the significant decrease of TRP plasma level and augmentation of concentration of its metabolites. The high concentrations of 3-hydroxykynurenine, xanthurenic acid, kynurenic acid, anthranilic acid and quinolinic acid positively correlated with degree of the renal insufficiency. Talking into account the biological properties of KYN metabolites, their accumulation in the blood, may be at least partially, responsible for severity of uremia as well as for uremic symptoms such as neuropathy, increased susceptibility to infections, hypertension, lipid disturbances and anemia.

4

Can kynurenine pathway tryptophan metabolites be used to monitor cadmium exposure?

100%

Pawlak D. , Brzoska M. , Zwierz K. , Stypulkowska A. , Moniuszko-Jakoniuk J.

Polish Journal of Environmental Studies

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2005

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tom 14

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nr 2

EN

We evaluated the possibility of using the urinary concentrations of tryptophan metabolites such as kynurenine (KYN) and kynurenic acid (KYNA) for monitoring cadmium (Cd) exposure and detecting early effects of its action in the kidney. For this purpose, we analyzed correlations between urinary excretion of both metabolites, Cd concentration and the activity of isoenzyme B of N-acetyl-β-D-glucosaminidase (NAG-B), recognized as one of the most sensitive markers of Cd nephrotoxicity. The study was conducted on rats using an experimental model, corresponding to human environmental and occupational exposure to Cd. The rats were administered 5 and 50 mg Cd/l of drinking water for 24 weeks. The administration of Cd resulted in a marked dose-dependent increase in KYN and KYNA elimination. Regression analysis revealed a linear correlation between urinary Cd concentration and KYN or KYNA excretion as well as between urinary NAG-B activity and KYN or KYNA elimination. We hypothesize that metabolites of tryptophan via kynurenine pathway such as KYN and especially KYNA can be used to monitor chronic exposure to Cd.

5

Effect of cadmium on the peripheral kynurenine pathway in rats

100%

Pawlak D. , Brzoska M. , Moniuszko-Jakoniuk J. , Stypulkowska A. , Zwierz K.

Polish Journal of Environmental Studies

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2005

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tom 14

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nr 4

EN

This study investigated the kynurenine metabolism in rats treated with cadmium. We used an animal model at the levels of Cd corresponding to human environmental and occupational exposure to this metal which allows the assessment of its early effect on the structure and function of kidneys. We observed significant decrease in the serum concentration of tryptophan (TRP) and its metabolites: kynurenine (KYN), kynurenic acid (KYNA), and 3-hydroxykynurenine (3-HKYN), which was accompanied by a decrease in KYN derivatives in kidney and liver tissues. This effect was dependent on the level of Cd exposure. Regression analysis showed negative correlations between blood concentrations of Cd and TRP derivatives in serum, kidney and liver tissues. Conversely, the urinary concentration of KYN and KYNA increased. Changes in product degradation of TRP after Cd treatment were proportional to the severity of renal damage and correlated with the concentration of proximal tubular injury marker — urinary isoenzyme B of N-acetyl-D-glucosaminidase (NAG-B). Our results seem to indicate that intoxication with Cd induced significant disturbances in the peripheral kynurenine pathway.

6

The valproic acid-induced effects on kynurenine pathway correlate with the changes in the central and peripheral concentration of amino acids

80%

Maciejak P. , Szyndler J. , Turzynska D. , Sobolewska A. , Kolosowska K. , Lehner M. , Wislowska-Stanek A. , Skorzewska A. , Hamed A. , Plaznik A.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

EN

Despite its widespread use, the mechanisms of valproic acid (VPA) action are not fully understood. In the current study, we have examined the peripheral and central effects of VPA administration on the metabolic pathway of tryptophan (TRP): concentration of its centrally active metabolites, kynurenine (KYN) and kynurenic acid (KYNA). Moreover, the role of a displacement of TRP from serum albumin binding sites, and changes in the peripheral and central concentration of amino acid including glutamate (GLU), GABA, alanine (ALA), glutamine (GLTM), glycine (GLY), aspartate (ASP), were also studied. We found that VPA administration produced a progressive and strong increase in the central concentration of KYNA, KYN and TRP. Simultaneously, TRP concentration in plasma declined while the peripheral increase of KYNA in plasma was weaker and occurred earlier than in the hippocampus. We also observed that administration of ibuprofen to rats, a prototypic drug used to study drug binding to serum albumin, strongly increased the amount of a free serum and hippocampal TRP concentration, to a degree similar to the effect of VPA. Moreover, we found that the most pronounced changes in the concentration of amino acids caused by administration of VPA include an increase of GLU and a decrease of ALA in the plasma as well as a decrease of ASP and an increase of GABA in the brain. The factor analysis revealed that the changes in the concentrations of TRP, determined both in the plasma and in the hippocampus grouped strongly with the changes in the plasma concentrations of GLU and the central concentration of ASP. Our results showed that administration of VPA strongly modifies the activity of the kynurenine pathway with significant changes in TRP, KYN and KYNA levels in the CNS. The reason for this may be a strong VPA-induced displacement of TRP from its binding sites to plasma albumin. It appears also that the changes in TRP evoked by VPA administration due to competition for transport into the brain, may result in a shift in the central and peripheral balance between branched-chain (BCAA) and aromatic amino acids (AAA). This may lead to a decrease in BCAA transport to the brain, leading to a deficit of BCAAs as a donor of amino groups to the process of GLU resynthesis from pyruvate. Changes in the BCAA/ AAA ratio, arising as a consequence of changes in the TRP level, could explain an observed increase in the plasma concentrations of GLU and a decrease in the ASP concentrations in the brain that occurred after administration of VPA. In sum, given the neuroprotective role of KYNA, the current study suggests that stimulation of the kynurenine pathway may also apply to the central and peripheral concentration of amino acids. The modification of the activity of the kynurenine pathway may at least in part contribute to the related antiepileptic and neuroprotective mechanisms of VPA action.

7

Metabolity indolowe jadalnego grzyba - gasowki nagiej [Lepista nuda] [Bull.:Fr] Cooke

60%

Kohlmunzer S. , Wegiel J.

Bromatologia i Chemia Toksykologiczna

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2001

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tom 34

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nr 1

85-90

PL

Badania owocników gąsówki nagiej Lepista nuda przeprowadzone za pomocą metod chromatograficznych i spektralnych wykazały obecność kwasowych pochodnych tryptofanu: kwasów 3-indolooctowego (IAA) i 3-indolopropionowego (IPrA) oraz produktów biochemicznej degradacji tryptofanu: kynureniny i 3-hydroksykynureniny. Dwa ostatnie produkty nie byty obecne w hodowli mycelialnej tego gatunku, która zawierała głównie kwas 3-indolooctowy i tryptofan.

EN

Indole secondary metabolites of the edible mushroom species Lepista nuda (Bull.: Fr.) Cooke carpophores were determined by several chromatographic (TLC, PTLC, HPLC) and spectral (EIMS, 1HNMR) methods. For comparison, the same metabolites were assayed in the mushroom mycelium cultivated in vitro. Two acids biogenetically related to tryptophan were detected in the mushroom carophores, i.e. 3-indoleacetic (IAA) and 3-indolepropionic (IPrA) acid. Besides, two other tryptophan degradation products were detected: kynurenine and 3-hydroxykynurenine. In the cultured mycelium, 3-indoleacetic acid was detected as the major metabolite, along with the native tryptophan aminoacid. The results may suggest that an enzymatic system capable of breaking down the pyrole ring of the indole structure is present in the carophores of the studied mushroom species.