A5009109440- Pharmacogenetics and Drug Metabolism
- Toxic Organic Pollutants Impact
- Drug Transport and Resistance Mechanisms
- Analytical Chemistry and Chromatography
- Effects and risks of endocrine disrupting chemicals
- Eicosanoids and Hypertension Pharmacology
- Gut microbiota and health
- Antibiotic Resistance in Bacteria
- Cancer therapeutics and mechanisms
- Hormonal Regulation and Hypertension
- Peptidase Inhibition and Analysis
- Carcinogens and Genotoxicity Assessment
- Drug-Induced Hepatotoxicity and Protection
- Metabolomics and Mass Spectrometry Studies
- Probiotics and Fermented Foods
- Ion channel regulation and function
- Diet, Metabolism, and Disease
- Reproductive System and Pregnancy
- Toxin Mechanisms and Immunotoxins
- Inflammatory mediators and NSAID effects
- Escherichia coli research studies
- Peroxisome Proliferator-Activated Receptors
- Plant Toxicity and Pharmacological Properties
- Antifungal resistance and susceptibility
- Epigenetics and DNA Methylation
Institute of Molecular and Translational Medicine
2016-2025
Palacký University Olomouc
2016-2025
Regional Centre of Advanced Technologies and Materials
2018-2019
Institute of Pharmacology
2014-2016
We examined the effects of gut microbial catabolites tryptophan on aryl hydrocarbon receptor (AhR). Using a reporter gene assay, we show that all studied are low-potency agonists human AhR. The efficacy differed substantially, comprising with no or low (i3-propionate, i3-acetate, i3-lactate, i3-aldehyde), medium (i3-ethanol, i3-acrylate, skatole, tryptamine), and high (indole, i3-acetamide, i3-pyruvate) efficacies. displayed ligand-selective antagonist activities by i3-pyruvate, i3-aldehyde,...
Abstract The human aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that pivotal regulator of physiology and pathophysiology. Allosteric inhibition AhR was previously thought to be untenable. Here, we identify carvones as noncompetitive, insurmountable antagonists characterize the structural functional consequences their binding. Carvones do not displace radiolabeled ligands from binding but instead bind allosterically within bHLH/PAS-A region AhR. influence...
Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and oxytoca pathogenicity. These closely related produce the enterotoxins tilimycin tilivalline; cytotoxin-producing strains are causative agent antibiotic-associated hemorrhagic colitis have been associated with necrotizing enterocolitis premature infants. We carbohydrates induce cytotoxin...
Abstract Background Siderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target pathophysiological mechanisms of pathogens. Gallium-68 replace in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific interactions play crucial role recognition receptors, transporters, and...
Acinetobacter baumannii (AB) is an opportunistic pathogen with growing clinical relevance due to its increasing level of antimicrobial resistance in the last few decades. In event AB hospital outbreak, fast detection and localization crucial, prevent further spread. However, contemporary diagnostic tools do not always meet requirements for rapid accurate diagnosis. For this reason, we report here possibility using gallium-68 labeled siderophores, bacterial iron chelators, positron emission...
1. The possibility of interaction isoflavonoids with concomitantly taken drugs to determined safety was studied. Inhibition nine forms cytochrome P450 (CYP3A4, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6 and CYP2E1) by 12 (daidzein, genistein, biochanin A, formononetin, glycitein, equol six glucosides, daidzin, puerarin, genistin, sissotrin, ononin glycitin) studied systematically.2. most potent inhibitors were genistein daidzein inhibiting noncompetitively the CYP2C9 Ki 35.95 ±...
Antifungal drug ketoconazole causes severe drug-drug interactions by influencing gene expression and catalytic activity of major drug-metabolizing enzyme cytochrome P450 CYP3A4. Ketoconazole is administered in the form racemic mixture two cis-enantiomers, i.e. (+)-ketoconazole (−)-ketoconazole. Many enantiopure drugs were introduced to human pharmacotherapy last decades. In current paper, we have examined effects cis-enantiomers on CYP3A4 hepatocytes HepG2 cells liver microsomes. We show...
Abstract Background Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the response. In non-small lung cancer (NSCLC), sensitivity treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated increase tumor infiltrating PD-1 + lymphocytes. Due solid heterogeneity populations, novel low molecular weight high-affinity diagnostic probes can reliability expression profiling lymphocytes (TILs) in tissue biopsies vivo mapping...
Amlodipine (AML) is available as a racemate, i.e., mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug-drug interactions between enantiomers. Enzyme inhibition evaluated using specific CYP substrates in human liver microsomes. With CYP3A, both enantiomers exhibited reversible time-dependent inhibition. S-AML stronger inhibitor midazolam hydroxylation: Ki values S- R-AML were 8.95 µM, 14.85 respectively. Computational...
Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they principally taken as many folk medicines and dietary supplements. The aim our study was to test compare potential inhibitory effect acyclic sesquiterpenes, trans-nerolidol, cis-nerolidol farnesol, on activities xenobiotic-metabolizing enzymes rat liver vitro. Rat subcellular fractions, relatively specific substrates,...
1. The aim of this work was to examine the differences in inhibitory potency individual enantiomers and racemic mixtures selected chiral drugs on human liver microsomal cytochromes P450.
The efforts for therapeutic targeting of the aryl hydrocarbon receptor (AhR) have emerged in recent years. We investigated effects available antimigraine triptan drugs, having an indole core their structure, on AhR signaling human hepatic and intestinal cells. Activation reporter gene assays was observed Avitriptan to a lesser extent Donitriptan, while other triptans were very weak or no activators AhR. Using competitive binding assay by homology docking, we identified as low-affinity ligand...
Herbal extracts represent a wide spectrum of biologically active ingredients with potential medical applications. By screening minor constituents jasmine essential oil towards aryl hydrocarbon receptor (AhR) activity using gene reporter assay (GRA), we found the antagonist effects jasmone (3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-one). It inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-, benzo[a]pyrene (BaP)-, and 6-formylindolo[3,2-b]carbazole (FICZ)-triggered AhR-dependent...
1. Itraconazole (ITZ), an antifungal azole derivate is a chiral drug that consists of four cis-diastereoisomers ((+)-2R,4S,2'R-ITZ-A; (+)-2R,4S,2'S-ITZ-B; (-)-2S,4R,2'S-ITZ-C and (-)-2S,4R,2'R-ITZ-D) which may differ in their pharmacokinetics pharmacodynamics. 2. As ITZ known as CYP3A4 inhibitor causing severe drug-drug interaction, the inhibitory potencies its individual optical isomers towards nine drug-metabolising cytochrome P450 (including CYP3A, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9,...
We developed and characterized a novel human luciferase reporter cell line for the assessment of peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity, PAZ-PPARg. The activity induced by PPARγ endogenous agonist 15d-PGJ2 prostaglandin PGD2 reached mean values (87.9 ± 14.0)-fold (89.6 19.7)-fold after 24 h exposure to 40 μM 70 PGD2, respectively. A concentration-dependent inhibition 15d-PGJ2- PGD2-induced was observed application T0070907, selective antagonist PPARγ,...
Abstract Background : Siderophores are small iron-binding molecules produced by microorganisms to facilitate iron acquisition from the environment. Radiolabelled siderophores offer a promising solution for infection imaging, as they can specifically target pathophysiological mechanisms of pathogens. Gallium-68 replace in siderophores, enabling molecular imaging with positron emission tomography (PET). Stereospecific interactions play crucial role recognition receptors, transporters, and...
Genetic polymorphism in cytochrome P450 (CYP) family of enzymes is a rather frequent cause serious problems with proper dosing drugs. This effect may be augmented by drug interaction between concomitantly taken drugs which are metabolized the same enzymes. The second interacting partner however easily compound natural origin as it case flavonoids from grapefruit juice. We examined prototypic isoflavonoid, genistein, on metabolism probe substrates genotypized human liver microsomes...
ABSTRACT Carvones, the constituents of essential oils dill, caraway, and spearmint, were reported to antagonize human aryl hydrocarbon receptor (AhR); however, exact molecular mechanism remains elusive. We show that carvones are non-competitive allosteric antagonists AhR inhibit induction target genes in a ligand-selective cell type-specific manner. Carvones do not displace radiolabeled ligand from binding at AhR, but they bind allosterically within bHLH/PAS-A region AhR. did influence...