Phase I metabolism of 3-methylindole, an environmental pollutant, by hepatic microsomes from carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss)
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26915592
DOI
10.1016/j.chemosphere.2016.02.037
PII: S0045-6535(16)30189-8
Knihovny.cz E-zdroje
- Klíčová slova
- 3-hydroxy-3-metyloxindole, 3-methylindole, Cytochrome P450, Hepatic microsomes, Indole-3-carbinol,
- MeSH
- chemické látky znečišťující vodu metabolismus toxicita MeSH
- druhová specificita MeSH
- elipticiny farmakologie MeSH
- I. fáze biotransformace MeSH
- indoly metabolismus MeSH
- inhibitory cytochromu P450 farmakologie MeSH
- jaterní mikrozomy účinky léků metabolismus MeSH
- játra účinky léků metabolismus MeSH
- kapři metabolismus MeSH
- ketokonazol farmakologie MeSH
- Oncorhynchus mykiss metabolismus MeSH
- oxindoly MeSH
- skatol metabolismus toxicita MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3-methyloxindole MeSH Prohlížeč
- chemické látky znečišťující vodu MeSH
- elipticiny MeSH
- ellipticine MeSH Prohlížeč
- indole-3-carbinol MeSH Prohlížeč
- indoly MeSH
- inhibitory cytochromu P450 MeSH
- ketokonazol MeSH
- oxindoly MeSH
- skatol MeSH
- systém (enzymů) cytochromů P-450 MeSH
We studied the in vitro metabolism of 3-methylindole (3MI) in hepatic microsomes from fish. Hepatic microsomes from juvenile and adult carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) were included in the study. Incubation of 3MI with hepatic microsomes revealed the time-dependent formation of two major metabolites, 3-methyloxindole (3MOI) and indole-3-carbinol (I3C). The rate of 3MOI production was similar in both species at both ages. No differences in kinetic parameters were observed (p = 0.799 for Vmax, and p = 0.809 for Km). Production of I3C was detected only in the microsomes from rainbow trout. Km values were similar in juvenile and adult fish (p = 0.957); Vmax was higher in juvenile rainbow trout compared with adults (p = 0.044). In rainbow trout and carp, ellipticine reduced formation of 3MOI up to 53.2% and 81.9% and ketoconazole up to 65.8% and 91.3%, respectively. The formation of I3C was reduced by 53.7% and 51.5% in the presence of the inhibitors ellipticine and ketoconazole, respectively. These findings suggest that the CYP450 isoforms CYP1A and CYP3A are at least partly responsible for 3MI metabolism. In summary, 3MI is metabolised in fish liver to 3MOI and I3C by CYP450, and formation of these metabolites might be species-dependent.
Product Quality Program IRTA Monells Girona Spain
University of South Bohemia in Ceske Budejovice Vodnany Czech Republic
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