• MeSH
• depresivní poruchy terapie   MeSH
• fenotyp MeSH
• finanční podpora výzkumu jako téma MeSH
• izoenzymy antagonisté a inhibitory   MeSH
• lidé MeSH
• mianserin analogy a deriváty   škodlivé účinky   terapeutické užití   MeSH
• paroxetin škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

Cílem projektu je upřesnění vztahů mezi genetickým základem pacienta, metabolickou kapacitou CYP 2D6 vzhledem k účinnosti a bezpečnosti léčby úzkostných poruch paroxetinem a stanovení délky přetrvávání inhibice CYP 2D6 po ukončení léčby paroxetinem.; The aim of the project is to establish the role of CYP 2D6 genetic polymorphism with to the efficacy and drug safety of treatment of anxiety disorders with paroxetine and duration of metabolic phenotype conversion within treatment discontinuation.

• MeSH
• alprazolam aplikace a dávkování   MeSH
• cytochrom P-450 CYP2D6 analýza   MeSH
• diagnostické techniky molekulární MeSH
• fenotyp MeSH
• paroxetin aplikace a dávkování   MeSH
• úzkostné poruchy farmakoterapie   MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• psychiatrie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• Publikační typ
• abstrakt z konference MeSH

Superfamily of cytochrome P450 enzymes (CYPs), a distinctive enzyme system by which human body defends itself against toxic compounds, is the subject of a complex regulation process involving various mechanisms, on the levels of expression and activity. Apart from physiological factors, several patho-physiological ones such as inflammation, infection, and stress affect CYP expression. The aim of this review is to summarize the current knowledge on the role of microtubules network in the regulation of drug metabolizing CYPs. Experiments on human and animal cell models revealed that microtubules disruption severely impaired basal and inducible expression of human CYP 1A1, 2B6, 2C8, 2C9, 2C19, and 3A4, and rat CYP 1A2, 2B1, 2B2, and 3A23. Inhibition of aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) transcriptional activity by microtubules disarray was found to be responsible for the suppressed CYP enzymes expression. However, the mechanism by which microtubules interfering agents (MIAs) inhibit GR and AhR transcriptional activities is not fully understood yet. Several lines of evidence indicate that: i) the cell cycle, G2/M phase in particular, has an influence on AhR and GR transcriptional activity, and ii) MIAs negatively modulate GR transcriptional activity via the activation of c-Jun-N-terminal kinase. In conclusion, down-regulation of major CYP enzymes by microtubules disarray is intriguing from the mechanistic point of view and in relation to the cell differentiation.

• MeSH
• biologické modely MeSH
• lidé MeSH
• mikrotubuly fyziologie   MeSH
• regulace genové exprese enzymů MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

1. The possibility of interaction of isoflavonoids with concomitantly taken drugs to determined isoflavonoids safety was studied. Inhibition of nine forms of cytochrome P450 (CYP3A4, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6 and CYP2E1) by 12 isoflavonoids (daidzein, genistein, biochanin A, formononetin, glycitein, equol and six glucosides, daidzin, puerarin, genistin, sissotrin, ononin and glycitin) was studied systematically. 2. The most potent inhibitors were genistein and daidzein inhibiting noncompetitively the CYP2C9 with Ki of 35.95 ± 6.96 and 60.56 ± 3.53 μmol/l and CYP3A4 (inhibited by genistein with Ki of 23.25 ± 5.85 μmol/l also by a noncompetitive mechanism). Potent inhibition of CYP3A4 was observed also with biochanin A (Ki of 57.69 ± 2.36 μmol/l) and equol (Ki of 38.47 ± 2.32 μmol/l). 3. Genistein and daidzein inhibit noncompetitively CYP3A4 and CYP2C9. With plasma levels in micromolar range, a clinically important interaction with concomitantly taken drugs does not seem to be probable.

• MeSH
• cytochrom P-450 CYP1A2 MeSH
• cytochrom P450 CYP2C19 MeSH
• glukosidy MeSH
• isoflavony metabolismus   MeSH
• jaterní mikrozomy enzymologie   MeSH
• játra enzymologie   MeSH
• lékové interakce MeSH
• lidé MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: The aim of the study was to find whether probiotic Lactobacillus casei influences the expression or the activity of cytochromes P450 (CYP) and whether it has an influence on the level of CYP mRNA in male rats. DESIGN: Live bacterial suspension of L. casei was administered orally (gavage) to healthy male Wistar rats daily for 7 days. Control group of rats was treated with the saline solution. Sections of the duodenum, jejunum, ileum, caecum and colon were dissected from each experimental animal. In all individual samples, the expression of selected CYPs was determined by Western blotting. The levels of expression of CYPs were also evaluated by mRNA using the real-time PCR method. RESULTS: There were changes observed in the expression of CYP enzymes and in the CYP mRNA levels along the intestine after application of L. casei. The expression of CYP1A1 enzyme was found to be decreased in the proximal part of the jejunum and colon, CYP1A1 mRNA level was decreased in the distal part of the jejunum, ileum and caecum. Thus, the changes in CYP1A1 protein or mRNA were observed along the intestine of male rats. Similarly, a decreased expression of the caecal CYP2E1 mRNA and of the duodenal CYP3A9 mRNA after treatment of rats with L. casei was found. CONCLUSION: Probiotic L. casei might be able to contribute to prevention against colorectal cancer by decreasing levels of certain forms of xenobiotic-metabolizing enzymes; moreover, in general, there is a possibility of interactions with concomitantly taken pharmacotherapeutic agents.

• MeSH
• aktivace enzymů účinky léků   MeSH
• aromatické hydroxylasy genetika   metabolismus   MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• cytochromy genetika   metabolismus   MeSH
• játra účinky léků   metabolismus   mikrobiologie   MeSH
• krysa rodu rattus MeSH
• Lactobacillus casei fyziologie   MeSH
• messenger RNA metabolismus   MeSH
• potkani Wistar MeSH
• probiotika farmakologie   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• steroid-16-alfa-hydroxylasa genetika   metabolismus   MeSH
• steroid-21-hydroxylasa genetika   metabolismus   MeSH
• střeva účinky léků   metabolismus   mikrobiologie   MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

Safranal and crocin are biologically active compounds isolated from Crocus sativus L., commonly known as saffron. Clinical trials confirm that saffron has antidepressant effect, thus being a potential valuable alternative in the treatment of depression. The aim of the present study was to determine, whether systemic administration of safranal and crocin can influence the metabolic activity of CYP3A, CYP2C11, CYP2B, and CYP2A in rat liver microsomes (RLM). The experiments were carried out on male Wistar albino rats intragastrically administered with safranal (4, 20, and 100 mg/kg/day) or with intraperitoneal injections of crocin (4, 20, and 100 mg/kg/day). Our results demonstrate the ability of safranal and crocin to increase the total protein content and to change the metabolic activity of several CYP enzymes assessed as CYP specific hydroxylations of testosterone in RLM. Crocin significantly decreased the metabolic activity of all selected CYP enzymes, while safranal significantly increased the metabolic activity of CYP2B, CYP2C11 and CYP3A enzymes. Therefore, both substances could increase the risk of interactions with co-administered substances metabolized by cytochrome P450 enzymes.

• MeSH
• aktivace enzymů účinky léků   fyziologie   MeSH
• Crocus * MeSH
• cyklohexeny izolace a purifikace   farmakologie   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• karotenoidy izolace a purifikace   farmakologie   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• rostlinné extrakty izolace a purifikace   farmakologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• terpeny izolace a purifikace   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• cytochrom P-450 CYP2D6 metabolismus   MeSH
• fenotyp MeSH
• lidé MeSH
• paroxetin škodlivé účinky   MeSH
• psychotropní léky metabolismus   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH

(-)-Linalool is the major floral scent occurring mainly in families Lamiaceae, Lauraceae and Rutaceae and is the main active compound of lavender oil. The purpose of this study was to reveal the influence of subchronic systemic treatment with (-)-linalool on the metabolic activity of CYP2A, 2B, 2C6, 2C11 and 3A in rat liver microsomes (RLM). The second aim was to reveal possible inhibitory effect of (-)-linalool on CYP2C6 in vitro. Wistar albino male rats were treated with (-)-linalool intragastrically at the doses of 40, 120, and 360 mg/kg/day for 13 days. Treatment with (-)-linalool at the dose of 360 mg/kg increased the metabolic activity of CYP2A assessed with testosterone as a probe substrate. (-)-Linalool showed weak competitive inhibition of CYP2C6 in rat liver microsomes, with IC(50) of 84 microM with use of diclofenac as a probe substrate.

• MeSH
• insekticidy farmakologie   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• játra účinky léků   enzymologie   MeSH
• krysa rodu rattus MeSH
• monoterpeny farmakologie   MeSH
• potkani Wistar MeSH
• systém (enzymů) cytochromů P-450 účinky léků   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antidepresiva druhé generace aplikace a dávkování   farmakokinetika   škodlivé účinky   MeSH
• cytochrom P-450 CYP2D6 genetika   metabolismus   MeSH
• depresivní poruchy enzymologie   epidemiologie   MeSH
• dospělí MeSH
• incidence MeSH
• libido účinky léků   MeSH
• lidé MeSH
• selektivní inhibitory zpětného vychytávání serotoninu farmakokinetika   MeSH
• sexuální dysfunkce psychické epidemiologie   chemicky indukované   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH