title: Verapamil does not modify catalytic activity of CYP450 in rainbow trout after long-term exposure.
abstract: Little is known about the effects of the cardiovascular drug verapamil (VRP) on metabolic processes in fish. Most calcium channel blockers including VRP are metabolized by cytochrome P450 (CYP450) enzymes. In this study we investigated the in vivo effect of VRP on some CYP450-mediated reactions in juvenile rainbow trout (Oncorhynchus mykiss). Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg l(-1)) for 0, 21, and 42 day. The following CYP450-mediated reactions were studied in hepatic microsomes: O-dealkylation of ethoxyresorufin, methoxyresorufin, and pentoxyresorufin, hydroxylation of coumarin, tolbutamide, and p-nitrophenol, and O-debenzylation of 7-benzyloxy-4-trifluoromethylcoumarin. The amounts of products of these reactions did not differ among fish exposed to different levels of VRP and control fish. This suggests that the levels of VPR used did not alter catalytic activity of the selected CYP450 enzymes. In conclusion, none of the investigated CYP450-mediated reactions has potential as a biomarker to monitor VRP contamination of the aquatic environment.
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, Vodnany 389 25, Czech Republic. Electronic address: vburkina@frov.jcu.cz.
authors.forename: V
authors.initials: V
authors.lastname: Burkina
authors.affiliation: Swedish University of Agricultural Sciences, Department of Food Science, Uppsala 750 07, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Zamaratskaia
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, Vodnany 389 25, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Randak
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, Vodnany 389 25, Czech Republic.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, Vodnany 389 25, Czech Republic.
authors.forename: G
authors.initials: G
authors.lastname: Fedorova
authors.affiliation: Swedish University of Agricultural Sciences, Department of Food Science, Uppsala 750 07, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Pickova
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, Vodnany 389 25, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Zlabek
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000633:toxicity*; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D017686:Oncorhynchus mykiss; D010078:Oxazines / Q000378:metabolism; D014700:Verapamil / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: C419147:7-benzyloxy-4-trifluoromethylcoumarin; D015415:Biomarkers; D002121:Calcium Channel Blockers; D003374:Coumarins; D009596:Nitrophenols; D010078:Oxazines; D014874:Water Pollutants, Chemical; C044943:pentoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D014700:Verapamil; C024836:4-nitrophenol