Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes. Techniques of gene reporter assays, qRT-PCR, Simple Western blotting by Sally Sue™ and electrophoretic mobility shift assay EMSA were employed. All compounds activated AhR, but their efficacies, potencies and dose-response profiles differed substantially. The strongest activators of AhR and inducers of CYP1A1 in HepG2 cells were DMU-212 ((E)-3,4,5,4´-tetramethoxystilbene), trans-piceatannol, cis-piceatannol, trans-trismethoxyresveratrol and trans-pinostilbene. While DMU-212 and trans-trismethoxyresveratrol also induced CYP1A1 and CYP1A2 in primary human hepatocytes, the effects of trans-piceatannol, cis-piceatannol and trans-pinostilbene weaned off. On the other hand, trans-4-methoxystilbene was strong CYP1A inducer in hepatocytes but not in HepG2 cells. Differences between effects of stilbenes in HepG2 cells and human hepatocytes are probably due to the extensive phase I and phase II xenobiotic metabolism in human hepatocytes. The data obtained may be of toxicological relevance.
- MeSH
- buňky Hep G2 účinky léků MeSH
- cytochrom P-450 CYP1A1 genetika MeSH
- cytochrom P-450 CYP1A2 genetika MeSH
- dospělí MeSH
- hepatocyty účinky léků MeSH
- induktory cytochromu P450 CYP1A2 chemie farmakologie MeSH
- isomerie MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- senioři MeSH
- stilbeny chemie farmakologie MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Epigallocatechin-3-gallate (EGCG) is widely used as a weight controlling supplement. Concerns about its safety evoked after cases of hepatotoxicity occurred upon its use. The underlying factors that could be involved in EGCG associated hepatotoxicity are not fully studied. In this study, we investigated the possible impact of lipopolysaccharide (LPS), as an inflammagen, on the effect of EGCG on hepatocytes. HepG2 cells were treated with different concentrations of EGCG (100, 200, 500 μM), with and without LPS (10 nM)-presensitization of the cells. Viability of HepG2 cells decreased with the increased concentrations of EGCG; the viability was even lesser in LPS-presensitized cells. Oxidative stress (Ox.LDL and CXCL16), the expression of nuclear retinoic receptors (RAR, RXR) and the biomarkers of hepatocellular injury (TNFα, TGFβ1) were all relatively higher in LPS-presensitized cells compared to non-sensitized cells upon treatment with EGCG. Sensitization of HepG2 cells with LPS alone did not affect the viability or any of the other biomarkers considered in this study. In conclusion, EGCG alone can be harmful to liver at high concentrations and this effect may become more pronounced under the influence of an inflammagen.
- Klíčová slova
- epigallocatechin-3-gallate (EGCG),
- MeSH
- buňky Hep G2 chemie imunologie účinky léků MeSH
- hepatocyty * chemie imunologie účinky léků MeSH
- katechin * analogy a deriváty farmakologie toxicita MeSH
- polyfenoly farmakologie toxicita MeSH
- techniky in vitro metody statistika a číselné údaje MeSH
- viabilita buněk účinky léků MeSH
- zánět * MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Hyperforin is a prenylated phloroglucinol derivative which occurs in the plant Hypericum perforatum L. It has several medicinally important properties (antidepressant, anti-inflammatory, proapoptotic, antibacterial and antiangiogenic). To enable its medicinal use, it is necessary to investigate its potential genotoxic effect on human cell lines. We also observed an anticlastogenic effect of hyperforin towards the indirect mutagen benzo(a)pyrene. Benzo(a)pyrene is a widespread polycyclic aromatic hydrocarbon. We performed experiments on human tumor cell line HepG2, using the in vitro mammalian chromosome aberration test. We investigated two cytogenic parameters: the number of aberrant metaphases and the total number of chromosome aberrations. We found out that hyperforin was not genotoxic on human cell line HepG2. The second part of our results implies that hyperforin had an anticlastogenic effect against the indirect mutagen benzo(a)pyrene in our experimental conditions. In future we will continue our research by using another range of hyperforin concentrations, other cell lines and other chemical mutagens.
- MeSH
- antidepresiva terapeutické užití toxicita MeSH
- antiflogistika terapeutické užití toxicita MeSH
- antimutagenní látky terapeutické užití toxicita MeSH
- benzopyreny * chemie MeSH
- biomedicínský výzkum MeSH
- buněčné linie cytologie účinky léků MeSH
- buňky Hep G2 cytologie účinky léků MeSH
- chromozomální aberace * chemicky indukované účinky léků MeSH
- lidé MeSH
- statistika jako téma MeSH
- třezalka * chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Organophosphorous compounds cause fatal intoxication based on inhibition of acetylcholinesterase, an essential enzyme of neurosynapses and neuromuscular junctions. There is an obvious need to develop appropriate treatment against them due to their application in agriculture and chemical industry or their misuse in terrorist or war attack. In the Czech army some medicaments have been established to be used against this poisoning; Obidoxime, Methoxime, Atropine and Benactyzine. In present in vitro study we focused on potential cytotoxic and genotoxic effect evaluation of these drugs by the clonogenic and comet assay, respectively. Obtained results show that oximes exhibit pronounced toxic effect, namely obidoxime in term of genotoxicity and methoxime in term of cytotoxicity.
- Klíčová slova
- Obidoxime, Methoxime, Atropine, Benactyzine,
- MeSH
- analýza kolonii tvořících jednotek metody statistika a číselné údaje MeSH
- antidota chemie MeSH
- buňky Hep G2 účinky léků MeSH
- časové faktory MeSH
- financování organizované MeSH
- kometový test metody statistika a číselné údaje MeSH
- organofosfáty otrava toxicita MeSH
- otrava farmakoterapie MeSH
- oximy chemie MeSH
- poškození DNA účinky léků MeSH
- reaktivátory cholinesterázy terapeutické užití MeSH
- Publikační typ
- techniky in vitro MeSH
