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Comparison of three fluorescent CYP3A substrates in two vertebrate models: pig and Atlantic salmon

Published online by Cambridge University Press:  11 November 2011

V. Zlabek  and
G. Zamaratskaia
V. Zlabek*
Affiliation:
Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25 Vodnany, Czech Republic
G. Zamaratskaia
Affiliation:
Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden
*
†E-mail: [email protected]
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Abstract

We investigated in vitro inhibitory effects of ketoconazole (KTZ) on cytochrome P450 activity in microsomes from pigs and Atlantic salmon. The following enzymatic reactions were studied: 7-benzyloxyresorufin and 7-ethoxyresorufin O-dealkylation (BROD and EROD, respectively), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD) and 7-benzyloxyquinoline O-debenzylation (BQOD). KTZ was a potent non-competitive inhibitor of BROD and BQOD in the microsomes from pigs, whereas in the microsomes from Atlantic salmon, these reactions were competitively inhibited by KTZ. BFCOD activity was inhibited by KTZ in a non-competitive manner in both species. KTZ non-competitively inhibited EROD in Atlantic salmon, but not in porcine microsomes. The activity of BROD and BQOD was higher in male than that in female pigs, but the activity of BFCOD showed no sex-related differences.

Keywords

ketoconazole7-ethoxyresorufin7-benzyloxyresorufin7-benzyloxy-4-trifluoromethylcoumarin7-benzyloxyquinoline
Type
Full Paper
Information
animal , Volume 6 , Issue 4 , April 2012 , pp. 633 - 640
Copyright
Copyright © The Animal Consortium 2011

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