Phase I metabolism of 3-methylindole, an environmental pollutant, by hepatic microsomes from carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss)
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26915592
DOI
10.1016/j.chemosphere.2016.02.037
PII: S0045-6535(16)30189-8
Knihovny.cz E-resources
- Keywords
- 3-hydroxy-3-metyloxindole, 3-methylindole, Cytochrome P450, Hepatic microsomes, Indole-3-carbinol,
- MeSH
- Water Pollutants, Chemical metabolism toxicity MeSH
- Species Specificity MeSH
- Ellipticines pharmacology MeSH
- Metabolic Detoxication, Phase I MeSH
- Indoles metabolism MeSH
- Cytochrome P-450 Enzyme Inhibitors pharmacology MeSH
- Microsomes, Liver drug effects metabolism MeSH
- Liver drug effects metabolism MeSH
- Carps metabolism MeSH
- Ketoconazole pharmacology MeSH
- Oncorhynchus mykiss metabolism MeSH
- Oxindoles MeSH
- Skatole metabolism toxicity MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3-methyloxindole MeSH Browser
- Water Pollutants, Chemical MeSH
- Ellipticines MeSH
- ellipticine MeSH Browser
- indole-3-carbinol MeSH Browser
- Indoles MeSH
- Cytochrome P-450 Enzyme Inhibitors MeSH
- Ketoconazole MeSH
- Oxindoles MeSH
- Skatole MeSH
- Cytochrome P-450 Enzyme System 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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