Effects of acetone, acetonitrile, ethanol, methanol and DMSO on cytochrome P450 in rainbow trout (Oncorhynchus mykiss) hepatic microsomes.
In vitro impacts of five organic solvents on cytochrome P450 (CYP450) enzyme activity were investigated using hepatic microsomes of rainbow trout. The rates of several CYP450-mediated reactions were investigated at solvent concentrations ranging from 0.01% to 3%. The solvents greatly affected all tested reactions. In at least 0.8% ethanol, 2% methanol or acetone, 1% acetonitrile or 3% dimethyl sulfoxide (DMSO), 7-ethoxyresorufin-O-deethylase (EROD) activity decreased and at 3% acetonitrile or ethanol, it was undetected. At 3%, all tested solvents except methanol reduced 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzylase (BFCOD) activity, but at low concentrations of ethanol (2% and lower) or DMSO (1% and lower), it was induced. This was not seen with the inclusion of a pre-incubation step. p-Nitrophenolhydroxylase (PNPH) activity was not affected at concentrations below 1% DMSO, and at 2% acetonitrile it was reduced, as it was above 1% methanol or 0.5% ethanol. Acetone did not affect PNPH activity with or without a pre-incubation step. In general, the degree of inhibition was similar with and without the pre-incubation step. We conclude that the concentration of organic solvent for solubilizing the substrate and inhibitor in in vitro microsomal studies should be minimized.
a Faculty of Fisheries and Protection of Waters , South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice , Vodnany , Czech Republic and.
Sidika
S
Sakalli
a Faculty of Fisheries and Protection of Waters , South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice , Vodnany , Czech Republic and.
Viktoriia
V
Burkina
a Faculty of Fisheries and Protection of Waters , South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice , Vodnany , Czech Republic and.
Vladimir
V
Zlabek
a Faculty of Fisheries and Protection of Waters , South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice , Vodnany , Czech Republic and.|b Department of Food Science , Uppsala BioCenter, Swedish University of Agricultural Sciences , Uppsala , Sweden.
Galia
G
Zamaratskaia
D000096:Acetone / Q000494:pharmacology*; D000097:Acetonitriles / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007527:Isoenzymes; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D000432:Methanol / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D012997:Solvents / Q000494:pharmacology*; D013379:Substrate Specificity
D000097:Acetonitriles; D007527:Isoenzymes; D012997:Solvents; D000096:Acetone; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000432:Methanol; D004121:Dimethyl Sulfoxide; C032159:acetonitrile
CYP1A1; CYP2E1; CYP3A; enzyme activity; organic solvent