In vitro inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) activities by sesamin in hepatic microsomes from two fish species.
In the present study, we investigated the effect of sesamin on CYP1A (7-ethoxyresorufin-O-deethylase, EROD) and CYP2E1-like activities (p-nitrophenol hydroxylase, PNPH) in hepatic microsomes obtained from Atlantic salmon (Salmo salar) and common carp (Cyprinus carpio). Addition of sesamin to the incubations in a concentration range from 1 to 200 μM decreased the activities of EROD and PNPH in a concentration dependent manner. It is likely that the inhibition of EROD was mechanism-based as demonstrated by the decrease in the IC50 value from 5.9 to 3.2 μM for A. salmon and from 7.9 to 3.0 μM for common carp when 5 min pre-incubation step was included. Similarly, PNPH activity was inhibited by sesamin with a decrease in the IC50 values from 61.7 to 15.2 μM for A. salmon and from 194.3 to 20.7 μM for common carp. Thus, our results indicated that sesamin can act as a mechanism-based inhibitor of EROD and PNPH activity with similar degree of inhibition in both fish species. More importantly, the inhibition of CYP1A, in addition to being mechanism-based, was competitive with K(i) value of 5.3 μM.
Department of Food Science, Uppsala BioCenter, Swedish University of Agricultural Sciences, P.O. Box 7051, 750 07 Uppsala, Sweden.
Liane
L
Wagner
Vladimir
V
Zlabek
Sofia
S
Trattner
Galia
G
Zamaratskaia
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002347:Carps; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004149:Dioxoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D017705:Lignans / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000737:chemistry*; D012474:Salmon
D000975:Antioxidants; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004149:Dioxoles; D017705:Lignans; D019363:Cytochrome P-450 CYP1A1; C054125:sesamin