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Tytuł:
Wybrane farmakokinetyczne interakcje leków w trakcie leczenia padaczki. Część II
Selected pharmacokinetic drug interactions during treatment of epilepsy. Part II
Autorzy:
Jastrzębski, Karol
Kacperska, Magdalena Justyna
Kozera-Kępiniak, Alicja
Klimek, Andrzej
Powiązania:
https://bibliotekanauki.pl/articles/1053388.pdf
Data publikacji:
2013
Wydawca:
Medical Communications
Tematy:
CYP2C19
CYP2C9
CYP2D6
CYP2E1
CYP3A4
UDP- glucuronosyltransferases
elimination
glucuronidation
metabolism of drugs
reaction of the second phase
the reaction of the first phase oxidation of drugs
valproic acid
metabolizm leków
reakcja pierwszej fazy
oksydacja leków
reakcja drugiej fazy
glukuronidacja
kwas walproinowy
eliminacja leku
UDP-glukuronylotransferazy
Opis:
Epilepsy is a disease of unknown cause to the end, mainly characterized by the occurrence of unprovoked seizures. A seizure is a temporary change, in turn, reactivity or physiological change in part or whole brain. Seizures are divided into partial, generalized and unclassified. The concept of drug-resistant epilepsy may seem somewhat obvious and intuitively understandable, but not yet developed a detailed definition of commonly accepted. As a result, doctors and researchers use very different criteria and, in some cases, even give up the precise criteria, which makes it difficult to compare the results of clinical trials and the development of practical guidelines. In the treatment of epilepsy, there is no one standard way to proceed. The aim of epilepsy treatment is complete seizure control and getting the least side effects during treatment with antiepileptic drugs. The drug should be tailored to the type of seizure or epilepsy syndrome, the frequency and severity of seizures. The choice depends on the type of drug seizures, for example, primary generalized seizures, valproic acid is used, and secondarily generalized seizures and partial carbamazepine. Older-generation drugs (phenytoin, phenobarbital, primidone) is slowly becoming obsolete. However, may be prescribed for specific indications. There is also a large group of new drugs (lamotrigine, vigabatrin, oxcarbazepine, gabapentin, levetiracetam, felbamat, topiramate, tiagabine), which are becoming increasingly popular. The emergence of a new generation of drugs gave them some advantage over older-generation drugs. They are characterized by greater specificity of action, improved pharmacokinetic properties, better evaluation of clinical trials and less side effects. These drugs are in clinical trials, and direct observation of lessons can be drawn that they are very useful in some types of epilepsy. There is no doubt that further research and observation. This article presents a brief overview of the pharmacokinetic properties of selected drugs as well as potential interactions between them. Properly processes of absorption, metabolism, distribution and elimination of drugs determine the appropriate therapeutic efficacy. The success of treatment can also significantly affect the pharmacokinetic and pharmacodynamic interactions.
Padaczka to choroba o nieznanej do końca etiologii, charakteryzująca się występowaniem nieprowokowanych napadów padaczkowych. Napad padaczkowy to z kolei przejściowa zmiana reaktywności lub zmiana stanu fizjologicznego części bądź całego mózgu. Napady dzielą się na: częściowe, uogólnione i niesklasyfikowane. Pojęcie padaczki lekoopornej może się wydawać oczywiste i zrozumiałe, niemniej jednak nie opracowano dotychczas powszechnie uznawanej szczegółowej definicji. W efekcie lekarze i badacze stosują bardzo różne kryteria, a w niektórych przypadkach nawet rezygnują z dokładnych kryteriów, co znacznie utrudnia porównywanie wyników badań klinicznych i tworzenie wytycznych. W leczeniu padaczki nie występuje jeden standardowy sposób postępowania. Celem terapii padaczki jest całkowita kontrola napadów i uzyskanie jak najmniejszych objawów niepożądanych podczas leczenia lekami przeciwpadaczkowymi. Lek powinien być dostosowany do typu napadu lub zespołu padaczkowego, częstości i ciężkości napadów. Wybór leków zależy od rodzaju napadów, przykładowo w napadach pierwotnych uogólnionych stosowany jest kwas walproinowy, natomiast we wtórnie uogólnionych i częściowych – karbamazepina. Leki starszej generacji (fenytoina, fenobarbital, prymidon) powoli wychodzą z użycia. Mogą być jednak przepisywane z powodu indywidualnych wskazań. Jest też bardzo duża grupa nowych leków (lamotrygina, wigabatryna, okskarbazepina, gabapentyna, lewetyracetam, felbamat, topiramat, tiagabina), które stają się coraz bardziej popularne. Pojawienie się leków nowej generacji dało im pewną przewagę w stosunku do starszych leków. Cechują je: większa swoistość działania, lepsze właściwości farmakokinetyczne, lepsza ocena klinicznych prób i słabsze objawy niepożądane. Z badań klinicznych i z bezpośrednich obserwacji wynika, iż są to leki bardzo przydatne w niektórych typach padaczek. Nie ulega wątpliwości, że potrzebne są dalsze badania i obserwacje. W niniejszym artykule przedstawiono krótki przegląd właściwości farmakokinetycznych wybranych leków, a także potencjalne interakcje między nimi. Prawidłowo przebiegające procesy wchłaniania, metabolizmu, dystrybucji i eliminacji leków warunkują odpowiednią skuteczność terapeutyczną. Na powodzenie leczenia mogą także znacząco wpłynąć interakcje farmakokinetyczne i farmakodynamiczne.
Źródło:
Aktualności Neurologiczne; 2013, 13, 1; 50-55
1641-9227
2451-0696
Pojawia się w:
Aktualności Neurologiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Tumor Anti-Initiation and Anti-Progression Properties of Sulphated-Extract of Colocasia esculenta
Autorzy:
Gamal-Eldeen, Amira M.
Amer, Hassan
Fahmy, Cinderella A.
Dahlawi, Haytham
Elesawy, Basem H.
Faizo, Nahla L.
Raafat, Bassem M.
Powiązania:
https://bibliotekanauki.pl/articles/2015590.pdf
Data publikacji:
2021-12-01
Wydawca:
Instytut Rozrodu Zwierząt i Badań Żywności Polskiej Akademii Nauk w Olsztynie
Tematy:
Colocasia esculenta
CYP1A
cancer chemoprevention & tumor anti-initiating
HDAC
macrophage function
breast MCF-7 carcinoma
Opis:
Colocasia esculenta (Taro) is an edible tuberous plant; however, corms are its most worldwide consumed part while the corm powder is widely used in food industries. In this work, a sulphated polysaccharide extract of C. esculenta corm (SCE) was prepared and its cancer chemopreventive properties was explored. The amending of carcinogen metabolism and radical scavenging affinity revealed that SCE is a strong tumor anti-initiation agent via suppressing cytochrome P450-1A and enhancing glutathione and the carcinogen detoxification enzyme; glutathione S-transferase. SCE exhibited a strong scavenging affinity towards critical radicals (hydroxyl and peroxyl). It induced lymphocyte growth and modulated the macrophage functions into an anti-inflammatory profile, via elevating macrophage proliferation and its binding affinity of fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS) and inhibiting nitric oxide and tumor necrosis factor-α generation. Furthermore, SCE showed a potent cytotoxicity against human breast MCF-7 carcinoma cells (IC50 27.73 µg/mL), whereas SCE treatment inhibited the activity of histone deacetylase (HDAC IC50 37.70 µg/mL) and disturbed the pattern of cell cycle phases. An arrest in both S- and G2/M-phases was linked with shifted cell populations towards late apoptosis and necrosis, as detected by flow cytometry. SCE is a promising cancer chemopreventive agent to be used in healthy food industries and for high breast cancer-risk population.
Źródło:
Polish Journal of Food and Nutrition Sciences; 2021, 71, 4; 393-401
1230-0322
2083-6007
Pojawia się w:
Polish Journal of Food and Nutrition Sciences
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The relationship between -C344/T aldosterone synthase (CYP11B2) gene polymorphism, enzyme activity level and increased risk of nonvalvular atrial fibrillation
Autorzy:
Yatskevich, Karsiaryna
Snezhitskiy, Viktor
Kurbat, Mikhail
Stepuro, Tatiana
Powiązania:
https://bibliotekanauki.pl/articles/552139.pdf
Data publikacji:
2015
Wydawca:
Stowarzyszenie Przyjaciół Medycyny Rodzinnej i Lekarzy Rodzinnych
Tematy:
atrial fibrillation, -C344/T aldosteronsynthase (CYP11B2) gene polymorphism
aldosterone synthase activity
Źródło:
Family Medicine & Primary Care Review; 2015, 2; 136-139
1734-3402
Pojawia się w:
Family Medicine & Primary Care Review
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The effect of indole-3-carbinol on the expression of CYP1A1, CYP1B1 and AhR genes and proliferation of MCF-7 cells
Autorzy:
Ociepa-Zawal, Marta
Rubiś, Błażej
Łaciński, Mariusz
Trzeciak, Wiesław
Powiązania:
https://bibliotekanauki.pl/articles/1041121.pdf
Data publikacji:
2007
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
p21
AhR
CYP
cell proliferation
estrone hydroxylation
xenoestrogens
Opis:
The influence of an antiestrogen, indole-3-carbinol (I3C) on the expression of CYP1A1, CYP1B1 and AhR genes was investigated in an attempt to establish whether I3C could increase the expression of genes involved in estrone metabolism. Another purpose was to examine the proliferation of an estrogen-dependent breast cancer cell (MCF-7 line) under the influence of I3C and both I3C and DDT. In MCF-7 cells incubated with I3C or I3C and DDT combined, quantitative RT-PCR analysis revealed a significant increase in the level of CYP1A1, AhR, and CYP1B1 transcripts. The proliferation rate of MCF-7 cells was increased by treatment with DDT or estradiol (E2), whereas I3C did not affect the proliferation of MCF-7 cells but greatly reduced the stimulatory effect of DDT, and abolished the effect of E2. The level of p21 transcript, encoding p21 protein involved in the cell cycle, was increased several-fold by I3C comparing to its level in cells incubated with estradiol or DDT. The results suggest that the proliferation of MCF-7 cells is accompanied not only by expression of genes encoding cytochromes involved in estrogen metabolism, but also by changes in the expression of other genes including that encoding p21 protein involved in the cell cycle.
Źródło:
Acta Biochimica Polonica; 2007, 54, 1; 113-117
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Temporal pattern of the induction of SF-1 gene expression by the signal transduction pathway involving 3',5'-cyclic adenosine monophosphate.
Autorzy:
Lehmann, Tomasz
Biernacka-Łukanty, Justyna
Saraco, Nora
Langlois, Dominique
Li, Jacques
Trzeciak, Wiesław
Powiązania:
https://bibliotekanauki.pl/articles/1041435.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
steroidogenensis
CYP11A1
Y-1 cells
SF-1
cAMP pathway
Opis:
The objective of our study was to investigate the effect of stimulation of the cAMP-dependent pathway on the expression of an orphan nuclear receptor, SF-1/Ad4BP in mouse adrenal tumour, Y-1 cells in culture. We evaluated the temporal pattern of the effects of corticotropin (ACTH) and the adenylyl cyclase activator forskolin on the level of SF-1 mRNA, and compared the time course of induction of SF-1 with that of CYP11A1. Forskolin, corticotropin and 8-Br-cAMP significantly elevated the level of the SF-1 transcript, after 1.5 h of incubation, with a concomitant increase of SF-1 protein level, observed after 6 h. The CYP11A1 transcript increased gradually over the incubation period, and reached the maximal level after 12 to 24 h. The steady-state level of the SF-1 transcript was unaffected by forskolin when the cells were incubated with actinomycin D, indicating that stimulation of the cAMP pathway results in enhanced transcription of the gene. The effect of forskolin was augmented by cycloheximide, suggesting that an inhibitory protein, whose synthesis was inhibited by cycloheximide, could be involved in negative regulation of SF-1 expression. It is concluded that SF-1 expression is positively regulated by the cAMP pathway at the transcriptional level, and can represent the primary event in cAMP-mediated induction of steroid hormone synthesis in Y-1 cells.
Źródło:
Acta Biochimica Polonica; 2005, 52, 2; 485-491
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Short-term heat stress effects on a cyp 11A1 canola plants
Autorzy:
Sakhno, L.
Slyvets, M.
Korol, N.
Karbovska, N.
Ostapchuk, A.
Kuchuk, M.
Powiązania:
https://bibliotekanauki.pl/articles/80876.pdf
Data publikacji:
2013
Wydawca:
Polska Akademia Nauk. Czytelnia Czasopism PAN
Tematy:
conference
abiotic stress
climate change
heat stress
cyp11A1 gene
nuclear genome
gene encoding
cytochrome P450-SCC
adrenal cortex mitochondrion
rape plant
Źródło:
BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology; 2013, 94, 3
0860-7796
Pojawia się w:
BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Rola 7α- hydroksylazy cholesterolu i genu CYP7A1 w fizjologii i patologii człowieka
Role of the cholesterol 7α- hydroxylase and CYP7A1 gene in human physiology and pathology
Autorzy:
Iwanicki, Tomasz
Balcerzyk, Anna
Żak, Iwona
Powiązania:
https://bibliotekanauki.pl/articles/1039371.pdf
Data publikacji:
2010
Wydawca:
Śląski Uniwersytet Medyczny w Katowicach
Tematy:
cyp7a1
kwasy żółciowe
cholesterol
polimorfizm
polymorphism
bile acids
Opis:
Cholesterol 7α- hydroxylase (CYP7A1) belongs to the big family of cytochrome p450. Biological significance of cholesterol 7α- hydroxylase is associated with beginning of cholesterol transformation to the bile acids. CYP7A1 affinity to the cholesterol is determined by its unique protein structure, different from the other proteins of cytochrome p450 family. CYP7A1 enzyme is enoded by CYP7A1 gene localized in short arm of chromosome 8. Expression of CYP7A1 gene could be regulated by farnesoid X receptor (FXR) or by kinases, which modulate nuclear receptor`s binding abilities to the gene promoter. Polymorphic variants and mutations present in the promoter region impact on the quality properties of the enzyme. CYP7A1 gene, encoding key enzyme of the cholesterol catabolic pathway is a main candidate to the research of its association with changes of serum lipids levels. Presence of genetic variants can be associated with changed levels of total cholesterol, triglycerides and Low- density lipoproteins (LDL). Promoter polymorphism of CYP7A1 is also main candidate for the research of association with such disease entities as gallbladder stone formation, colon cancer, gallbladder cancer or atherogenic- based diseases.
7α- hydroksylaza cholesterolu (CYP7A1) jest enzymem należącym do dużej rodziny cytochromu p450. Znaczenie biologiczne 7α- hydroksylazy cholesterolu związane jest z rozpoczęciem szeregu przemian cholesterolu do kwasów żółciowych. Powinowactwo CYP7A1 do cholesterolu determinowane jest unikalną budową białka, odmienną od reszty białek rodziny cytochromu p450. Enzym ten kodowany jest przez gen CYP7A1, którego locus znajduje się na ramieniu krótkim chromosomu ósmego. Ekspresja tego genu może być regulowana przy udziale farnezylowego receptora X (FXR), bądź zachodzić poprzez szereg kinaz białkowych, modulujących zdolność przyłączania się swoistych receptorów jądrowych do promotora CYP7A1. Warianty polimorficzne i mutacje, występujące w regionie promotorowym, wpływają na właściwości jakościowe enzymu. Gen CYP7A1, kodując kluczowy enzym w katabolizmie cholesterolu, jest głównym kandydatem do badań jego związku ze zmianami w osoczowym poziomie lipoprotein. Obecność wariantów genetycznych w promotorze genu CYP7A1 może być związana ze zmienionym poziomem cholesterolu całkowitego, triacylogliceroli czy LDL (Low- Density Lipoprotein). Polimorfizm promotora genu kodującego kluczowy enzym szlaku syntezy kwasów żółciowych i usuwania cholesterolu z organizmu jest głównym kandydatem do badań asocjacyjnych z takimi jednostkami chorobowymi, jak kamica żółciowa, nowotwory jelita grubego i woreczka żółciowego czy choroby o podłożu miażdżycowym.
Źródło:
Annales Academiae Medicae Silesiensis; 2010, 64, 3-4; 48-57
1734-025X
Pojawia się w:
Annales Academiae Medicae Silesiensis
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Relative quantification of CYP1A gene expression in whitefish (Coregonus lavaretus) exposed to benzo[a]pyrene
Autorzy:
Brzuzan, P.
Jurczyk, Ł.
Łuczyński, M. K.
Góra, M.
Powiązania:
https://bibliotekanauki.pl/articles/363188.pdf
Data publikacji:
2005
Wydawca:
Uniwersytet Warmińsko-Mazurski w Olsztynie
Tematy:
ekspresja genu CYP1A
sieja
benzo(a)piren
real-time PCR
benzo(a)pyrene
Coregonus lavaretus
CYP1A gene expression
RealTime PCR
relative quantification
Opis:
The expression of CYP1A (cytochrome P4501A) can be induced by a number of aromatic compounds in teleost fishes. We developed a real-time PCR assay for measuring relative quantities (RQ) of CYP1A mRNA in whitefish (Coregonus lavaretus). To test for the usefulness of the assay we performed a treatment study, using benzo[a]pyrene (B[a]P) a model CYP1A inducer. Primers for the CYP1A gene were adapted from the literature, whereas those for [beta]-actin (endogenous control) were designed from a region that was found to be conserved among salmonid [beta]-actin genes. A group of hatchery raised whitefish, with an average body mass of 15 g and total length of 12 cm were given an intraperitoneal injection (10 mg/kg) of B[a]P in corn oil (2 mg B[a]P/ml corn oil) or corn oil alone (Control). After 48 h, whitefish liver, head kidney and brains were collected for mRNA isolation and analysis. In all three tissues sampled, CYP1A mRNA was affected by treatment with B[a]P. Head kidney tissue showed the greatest induction potential (RQ=11.00) from base levels (RQ=1.00), followed by liver (RQ=9.45), and brain (RQ=3.76). These results demonstrated that CYP1A was highly inducible by B[a]P in whitefish head kidney and liver, and to some extent, in brain tissue. The approach presented here has the advantage of providing rapid and accurate measures of CYP1A induction in various tissues of fish responding to PAH contaminant exposure.
Źródło:
Environmental Biotechnology; 2005, 1, 1; 11-15
1734-4964
Pojawia się w:
Environmental Biotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Relation of the polymorphism of cyp51A sequence and the susceptibility of Aspergillus fumigatus isolates to triazoles determined by commercial gradient test (Etest) and by reference methods
Autorzy:
Nawrot, Urszula
Sulik-Tyszka, Beata
Kurzyk, Ewelina
Mroczyńska, Martyna
Włodarczyk, Katarzyna
Wróblewska, Marta
Basak, Grzegorz
Brillowska-Dąbrowska, Anna
Powiązania:
https://bibliotekanauki.pl/articles/1038548.pdf
Data publikacji:
2017
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Aspergillus fumigatus
triazole resistance
susceptibility testing
Etest
cyp51A sequence
Opis:
The aim of this study was to evaluate the accuracy of commercial gradient test (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates using reference microdilution methods and the analysis of sequences of the cyp 51A gene. The study was performed on twenty clinical isolates which were identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2 fragment of ribosomal DNA and the β-tubulin gene, out of them seventeen isolates showed wild-type cyp51A sequence and three were positive for the mutation TR34/L98H. All isolates were tested for the susceptibility to itraconazole (ITZ), voriconazole (VOR) and posaconasole (POS) using microdilution methods, according to EUCAST and CLSI protocols, as well as using Etest. The results of microdilution and Etests were analysed separately according to clinical breakpoints (CBP) defined by EUCAST version 7.0 and epidemiological cut off values (ECV). Etest as well as reference methods excellently recognised the WT isolates, which were susceptible to all tested triazoles, regardless of the method and CBP or ECV criteria used. The Etest recognized three non-WT isolates as resistant or intermediately sensitive to ITZ and POS and one as resistant to VOR. The categorical concordance between Etests and EUCAST and Etests and the CLSI method ranged from 90 to 100%. The interpretation of the results obtained from routine A. fumigatus Etests requires great caution. The use of the confirmative examinations with reference AST methods as well as with molecular tests is recommended.
Źródło:
Acta Biochimica Polonica; 2017, 64, 4; 631-634
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice
Autorzy:
Xie, Qing
Guo, Fang-Fang
Zhou, Wen
Powiązania:
https://bibliotekanauki.pl/articles/1039746.pdf
Data publikacji:
2012
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
carbon tetrachloride
cassia seed extract
antioxidant
CYP2E1
hepatoprotective effects
Opis:
Oxidative stress has been recognized as a critical pathogenetic mechanism for the initiation and the progression of hepatic injury in a variety of liver disorders. Antioxidants, including many natural compounds or extracts, have been used to cope with liver disorders. The present study was designed to investigate the hepatoprotective effects of cassia seed ethanol extract (CSE) in carbon tetrachloride (CCl4)-induced liver injury in mice. The animals were pre-treated with different doses of CSE (0.5, 1.0, 2.0 g/kg body weight) or distilled water for 5 days, then were injected intraperitoneally with CCl4 (0.1% in corn oil, v/v, 20 ml/kg body weight), and sacrificed at 16 hours after CCl4 exposure. The serum aminotransferase activities, histopathological changes, hepatic and mitochondrial antioxidant indexes, and cytochrome P450 2E1 (CYP2E1) activities were examined. Consistent with previous studies, acute CCl4 administration caused great lesion to the liver, shown by the elevation of the serum aminotransferase activities, mitochondria membrane permeability transition (MPT), and the ballooning degeneration of hepatocytes. However, these adverse effects were all significantly inhibited by CSE pretreatment. CCl4-induced decrease of the CYP2E1 activity was dose-dependently inhibited by CSE pretreatment. Furthermore, CSE dramatically decreased the hepatic and mitochondrial malondialdehyde (MDA) levels, increased the hepatic and mitochondrial glutathione (GSH) levels, and restored the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione S-transferase (GST). These results suggested that CSE could protect mice against CCl4-induced liver injury via enhancement of the antioxidant capacity.
Źródło:
Acta Biochimica Polonica; 2012, 59, 2; 265-270
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Preliminary study on adverse effects of phenanthrene and its methyl and phenyl derivatives in larval zebrafish, Danio rerio
Autorzy:
Wolińska, L.
Brzuzan, P.
Woźny, M.
Góra, M.
Łuczyński, M. K.
Podlasz, P.
Kolwicz, S.
Piasecka, A.
Powiązania:
https://bibliotekanauki.pl/articles/363152.pdf
Data publikacji:
2011
Wydawca:
Uniwersytet Warmińsko-Mazurski w Olsztynie
Tematy:
toksyczność ostra
CYP1A
cyp1b1
geny vtg
ekspresja mRNA
stężenie nie wywołujące efektu
WWA
Real-Time qPCR
acute toxicity
cyp1a genes
cyp1b1 genes
vtg genes
mRNA expression
No Effect Concentration
PAHs
Opis:
Toxic effects of polycyclic aromatic hydrocarbons (PAHs) have been extensively studied in fish, although knowledge concerning biological activities of phenanthrene and its derivatives remains still incomplete. The aim of this work was to evaluate lethal and sublethal effects of benzo(a)pyrene, phenanthrene and phenanthrene derivatives (1-methylphenanthrene, 4-methylphenanthrene, 1-phenylphenanthrene and 4-phenylphenanthrene) on zebrafish (Danio rerio) larvae. We conducted acute toxicity test, using 96h static renewal exposure to a series of the PAH concentrations (0.05, 0.50, 5.00, 50.00µmol*l-1), to determine the No Effect Concentration (NEC) value for each compound examined. The mean NEC estimates obtained in the study were 5.16۪.45µmol*l-1 (B[a]P), 4.88۪.13µmol*l-1 (Ph), 40.24䔰.93µmol*l-1 (1P-Ph), 47.92ۭ.61µmol*l-1 (1M-Ph), 24.31۱.33µmol*l-1 (4P-Ph) and 3.11۫.01µmol*l-1 (4M-Ph) and suggested the following order of PAH toxicities on Danio rerio larvae: 4M-Ph>Ph˜B[a]P>4PPhP-Ph>1M-Ph. To gain insight into possible molecular mechanisms of apparent toxicity of phenanthrene derivatives on zebrafish larvae, we examined mRNA expression of cyp1a, cyp1b1, and vtg genes in the larvae exposed for 48h to a PAH concentration of 0.50µmol*l-1. Whereas the larvae exposed to each tested PAH displayed many developmental abnormalities (i.e. pericardial and yolk sac edema, dorsal curvature, or tail malformations), no significant upregulation of cyp1a and cyp1b1 mRNA was observed, except for zebrafish exposed to B[a]P. However, significant reduction of vtg mRNA was observed in the larvae exposed to phenanthrene and its 4P- derivative. The results may contribute to the development of a new knowledge about effects of structurally diverse phenanthrene derivatives on vertebrate organisms.
Źródło:
Environmental Biotechnology; 2011, 7, 1; 26-33
1734-4964
Pojawia się w:
Environmental Biotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Polimorfizm genetyczny wybranych alleli cytochromu CYP2D6 u pacjentów z kardiomiopatią rozstrzeniową i zapaleniem mięśnia sercowego
Genetical polymporphism of chosen CYP2D6 alleles among the patients with dilated cardiomyopathy and myocarditis
Autorzy:
Smolik, Sławomir
Domal-Kwiatkowska, Dorota
Węglarz, Ludmiła
Powiązania:
https://bibliotekanauki.pl/articles/1038397.pdf
Data publikacji:
2011
Wydawca:
Śląski Uniwersytet Medyczny w Katowicach
Tematy:
cytochrom p-450
genotypowanie
wolny metabolizer
polimorfizm cyp2d6
Opis:
Cytochrome P450 2D6 has been reported to possess variation in the encoding gene that aff ects enzymatic activity. Interindividual diff erences in CYP2D6 activity can produce adverse eff ects or lack of therapeutic eff ect under standard therapy. The aim of the study was to genotyope the chosen alleles of CYP2D6 among the patients with clinically confi rmed myocarditis or dilated cardiomyopathy. Tetra-primer PCR assays was used to detect mutations in CYP2D6 *3, *4 and *6 allelles among 53 patients. A multiplex long PCR was used to genotype CYP2D6*5 allele. Analysis showed the presence of one heterozygote for CYP2D6*3, two heterozygote for CYP2D6*6, ten heterozygote and two homozygote for CYP2D6*4 among the examined patients. One person with deletion of CYP2D6 locus was also detected. Presented methods will facilitate and accelerate the detailed pharmacogenomic analysis of CYP2D6.
Cytochrom CYP2D6 ma różne warianty sekwencji kodującego go genu, wpływające na jego aktywność enzymatyczną. Międzyosobnicze różnice w aktywności izoenzymu CYP2D6 mogą prowadzić do działań niepożądanych lub braku skuteczności terapeutycznej standardowych dawek leku. Celem pracy było genotypowanie wybranych alleli CYP2D6 w grupie pacjentów z potwierdzonym klinicznie stanem zapalnym mięśnia sercowego lub kardiomiopatią rozstrzeniową. W pracy zastosowano reakcję PCR z użyciem czterech starterów w celu detekcji alleli 3*,4* i 6* CYP2D6 w grupie 53 pacjentów. Do wykrycia allelu CY2D6*5 zastosowano długołańcuchową reakcję PCR typu multipleks. Przeprowadzona analiza wykazała w badanej grupie pacjentów obecność jednej heterozygoty dla allelu CYP2D6*3, dwóch heterozygot dla allelu CYP2D*6, dziesięciu heterozygot i dwóch homozygot dla alellu CYP2D6*4. Znaleziono także jedną osobę z delecją locus CYP2D6. Przedstawione metody ułatwiają i przyspieszają dokładną analizę farmakogenetyczną izoformy CYP2D6.
Źródło:
Annales Academiae Medicae Silesiensis; 2011, 65, 3; 34-40
1734-025X
Pojawia się w:
Annales Academiae Medicae Silesiensis
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Phenobarbital-induced expression of cytochrome P450 genes.
Autorzy:
Czekaj, Piotr
Powiązania:
https://bibliotekanauki.pl/articles/1044233.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP2B
cytochrome P450
phenobarbital-responsive enhancer unit
CYP2H1.
orphan receptors
CYP3A
PXR
CAR
phenobarbital
Opis:
In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1093-1105
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Inhibition of CYP17 expression by adrenal androgens and transforming growth factor β in adrenocortical cells.
Autorzy:
Biernacka-Łukanty, Justyna
Lehmann, Tomasz
Trzeciak, Wiesław
Powiązania:
https://bibliotekanauki.pl/articles/1041500.pdf
Data publikacji:
2004
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP17
adrenocortical cells
TGF-β
androgens
expression
Opis:
Cytochrome P450c17, encoded by the CYP17 gene, is a component of the 17a-hydroxylase/17,20-lyase enzyme complex essential for production of adrenal glucocorticoids and androgens as well as gonadal androgens. The expression of CYP17 in adrenocortical cells is stimulated by corticotropin (ACTH) via the signal transduction pathway involving cAMP and protein kinase A (PKA). Thus, in addition to glucocorticoids, ACTH stimulates formation of adrenal androgens, which are known to induce transforming growth factor β (TGF-β) secretion. TGF-β in turn inhibits steroid hormone output by attenuating both basal and ACTH-dependent expression of CYP17. The present study revealed that treatment of bovine and human H295R adrenocortical cells with androgens resulted in a decrease in the basal level of CYP17 transcript and cortisol secretion, without affecting forskolin-stimulated levels. We also demonstrated that in H295R cells TGF-β inhibited both basal and forskolin-stimulated accumulation of CYP17 mRNA. Determination of promoter activity, directing luciferase reporter gene expression in H295R cells transfected with deletion fragments of bovine CYP17 promoter, indicated that the -483 to -433 bp fragment of the promoter was necessary for the inhibitory action of TGF-β on CYP17 expression. It is concluded that in bovine and human adrenocortical cells, androgens inhibit basal CYP17 expression probably at the transcriptional level and independently of the effect of TGF-β.
Źródło:
Acta Biochimica Polonica; 2004, 51, 4; 907-917
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
In Vitro approach for identification of a leading cytochrome P450 isoenzyme responsible for biotransformation of novel arylpiperazine drug candidates and their inhibition potency towards CYP3A4.
Autorzy:
Ulenberg, Szymon
Belka, Mariusz
Georgiev, Paweł
Król, Marek
Herold, Franciszek
Bączek, Tomasz
Powiązania:
https://bibliotekanauki.pl/articles/895671.pdf
Data publikacji:
2020-02-29
Wydawca:
Polskie Towarzystwo Farmaceutyczne
Tematy:
cytochrome P-450
drug-drug interactions
isoform
arylpiperazine
CYP 3A4 inhibitor
metabolic stability
Opis:
Presented article is a follow-up study of previous work, published in PLoS ONE in 2015 regarding metabolic stability of arylpiperazine derivatives, a very promising group of novel antidepressants. The aim of this study was to identify cytochrome P450 (CYP) isoforms that participate in the metabolism of some novel arylpiperazine derivatives developed by authors as well as their potency to inhibit reactions catalysed by identified lead metabolizing enzyme. Such studies allow to predict possible drug-drug interactions that might occur during co-administration of studied compounds with other drugs that are metabolized by identified enzyme. The compounds were incubated in vitro together with the isolated CYP isoforms. After the incubation, samples were analyzed by liquid chromatography coupled with mass spectrometry. The results showed main contribution of CYP3A4 isoform in biotransformation of the investigated derivatives. With CYP3A4 being the main CYP isoform responsible for the metabolism of arylpiperazine derivatives and at the same time being the main metabolizing enzyme for almost 50% of all drugs, a high chance of in vivo drug-drug interactions emerged. Therefore, IC50 values were also determined using testosterone hydroxylation as a probe reaction, specific for CYP3A4. The resulting values ranged from 6.13 to 15.85 µM, which places studied derivatives as moderate or weak inhibitors of CYP3A4. Those results, combined with conclusion that all of the arylpiperazine derivatives are also metabolized to some extent by other CYP isoforms (providing alternative metabolic pathways), result in conclusion that studied arylpiperazines might be safe for co-administration with other CYP3A4 substrates.
Źródło:
Acta Poloniae Pharmaceutica - Drug Research; 2020, 77, 1; 69-76
0001-6837
2353-5288
Pojawia się w:
Acta Poloniae Pharmaceutica - Drug Research
Dostawca treści:
Biblioteka Nauki
Artykuł

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