Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples
Language English Country Netherlands Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
9443853
Knihovny.cz E-resources
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Cytochrome P-450 CYP3A MeSH
- Isoenzymes metabolism MeSH
- Microsomes, Liver enzymology MeSH
- Catalysis MeSH
- Humans MeSH
- Swine, Miniature metabolism MeSH
- Nifedipine antagonists & inhibitors metabolism MeSH
- Oxidation-Reduction drug effects MeSH
- Swine MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Troleandomycin pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- CYP3A protein, human MeSH Browser
- CYP3A4 protein, human MeSH Browser
- Cytochrome P-450 CYP3A MeSH
- Isoenzymes MeSH
- Nifedipine MeSH
- Cytochrome P-450 Enzyme System MeSH
- Troleandomycin MeSH
Cytochrome P450 (CYP) of the 3A family (CYP3A) has been detected in minipig liver microsomes by immunochemical screening (Western blotting), revealing bands that co-migrate with human CYP3A4 and 3A5. The nifedipine oxidase activity and testosterone 6beta-hydroxylating activity (specific markers for CYP3A enzymes) of the human liver microsomal and minipig liver microsomal samples were comparable, as were the results of specific inhibition of this activity by triacetyloleandomycin. The presence of CYP1A, 2A, 2C, 2D, and 2E1 marker activities in minipig liver microsomes was found by testing with the respective specific substrates (7-ethoxyresorufin, coumarin, tolbutamide, bufuralol, and chlorzoxazone). 7-Pentoxyresorufin O-depentylase activity (indicative of CYP2B) was absent from minipig as well as human liver microsomal samples. The results indicate that minipigs might be, in many cases, the most suitable experimental animals to predict biotransformation pathways in humans, because the activity of the most important CYP isoform in humans (CYP3A, metabolizing the majority of known drug substrates) is present in minipigs, with comparable levels and activities. Moreover, there is no need to induce CYP enzyme levels.
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