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SHR Neuro Cancer Cardio Lipid Metab Microb
Frohlich, E; Kueznik, T; Samberger, C; Roblegg, E; Wrighton, C; Pieber, TR.
Size-dependent effects of nanoparticles on the activity of cytochrome P450 isoenzymes.
TOXICOL APPL PHARMACOL. 2010; 242(3): 326-332.
Doi: 10.1016/j.taap.2009.11.002
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Fröhlich Eleonore
- Co-authors Med Uni Graz
- Kolesnik Tatjana
- Meindl Claudia
- Pieber Thomas
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- Abstract:
- Nanoparticles are known to be able to interfere with cellular metabolism and to cause cytotoxicity and moreover may interfere with specific cellular functions. Serious effects on the latter include changes in liver cell function. The cytochrome P450 system is expressed in many cells but is especially important in hepatocytes and hormone-producing cells. The interaction of polystyrene nanoparticles with the most important drug-metabolizing cytochrome P450 isoenzymes, CYP3A4, CYP2D6, CYP2C9 and CYP2A1 expressed individually in insect cells (BACULOSOMES was studied by the cleavage of substrates coupled to a fluorescent dye. The data obtained for individual isoenzymes were compared to metabolism in microsomes isolated from normal liver and from the hepatoma cell line H4-II-E-C3. Small (20-60 nm) carboxyl polystyrene particles but not larger (200 nm) ones reached high intracellular concentrations in the vicinity of the endoplasmic reticulum. These small particles inhibited the enzymatic activity of CYP450 isoenzymes in BACULOSOMES and substrate cleavage in normal liver microsomes. They moreover increased the effect of known inhibitors of the cytochrome P450 system (cimetidine, phenobarbital and paclitaxel). Substrate cleavage by the hepatoma cell line H4-II-E-C3 in contrast was undetectable, making this cell line unsuitable for this type of study. Our results thus demonstrate that nanoparticles can inhibit the metabolism of xenobiotics by the CYP450 system in model systems in vitro. Such inhibition could also potentially occur in vivo and possibly cause adverse effects in persons receiving medication.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - metabolism
- Cell Line, Tumor -
- Cytochrome P-450 Enzyme System - antagonists and inhibitors Cytochrome P-450 Enzyme System - metabolism
- Drug Interactions -
- Endoplasmic Reticulum - metabolism
- Enzyme Inhibitors - pharmacology
- Fluorescent Dyes - chemistry
- Insects -
- Isoenzymes -
- Liver Neoplasms - enzymology Liver Neoplasms - metabolism
- Microsomes, Liver - enzymology Microsomes, Liver - metabolism
- Nanoparticles -
- Particle Size -
- Polystyrenes - chemistry
- Rats -
- Transfection -
- Xenobiotics - metabolism
- Find related publications in this database (Keywords)
- Nanoparticles
- Drug metabolism
- Cytochrome P450 isoenzymes