title: Does dexamethasone affect hepatic CYP450 system of fish? Semi-static in-vivo experiment on juvenile rainbow trout.
abstract: Effects of aquatic pollutants on fish are of increasing concern. Pharmaceutical-based contaminants are prioritized for further study in environmental risk assessment using several approaches. Dexamethasone (DEX) was one such contaminant recognised for its effect on fish health status. Thus, we carried out an in vivo experiment to identify potential effects of DEX on rainbow trout. Fish were exposed to 3, 30, 300 and 3000ngL(-1) DEX in a semi-static system over a period of 42d. The concentrations of DEX that fish were exposed to was confirmed by LC-LC-MS/MS. Using hepatic microsomes, we determined cytochrome P450 content, activities of ethoxyresorufin O-deethylase (EROD), p-nitrophenol hydroxylase (PNPH), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) and benzyloxyquinoline O-debenzylase (BQOD), as well as protein expression. Our results showed that fish do not change the catalytic activity of CYP450-mediated reactions after high DEX concentration exposure. These results disagree with mammalian studies, where DEX is a well-known inducer of CYP450. We showed a significant effect of DEX exposure on CYP450-mediated reactions (EROD, BCFOD, BQOD and PNPH) when expressed as amount of product formed per min per nmol total CYP450 at 3, 30 and 300ngL(-1) after 21d exposure. Moreover, BFCOD and BQ activities showed matching trends in all groups. Western blot analysis showed induction of CYP3A-like protein in the presence of the lowest environmentally relevant concentration of DEX. Based on these findings, continued investigation of the effect of DEX on fish using a battery of complementary biomarkers of exposure and effect is highly relevant.
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, 389 25 Vodnany, Czech Republic. Electronic address: vburkina@frov.jcu.cz.
authors.forename: Viktoriia
authors.initials: V
authors.lastname: Burkina
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, 389 25 Vodnany, Czech Republic. Electronic address: sakalli@frov.jcu.cz.
authors.forename: Sidika
authors.initials: S
authors.lastname: Sakalli
authors.affiliation: Department of Food Science, Aarhus University, P.O. Box 50, DK-8830 Tjele, Denmark. Electronic address: Martink.rasmussen@food.au.dk.
authors.forename: Martin Krøyer
authors.initials: MK
authors.lastname: Rasmussen
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, 389 25 Vodnany, Czech Republic; Swedish University of Agricultural Sciences, Uppsala BioCenter, Department of Food Science, P.O. Box 7051, SE-750 07 Uppsala, Sweden. Electronic address: Galia.Zamaratskaia@slu.se.
authors.forename: Galia
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, 389 25 Vodnany, Czech Republic. Electronic address: okoba@frov.jcu.cz.
authors.forename: Olga
authors.initials: O
authors.lastname: Koba
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, 389 25 Vodnany, Czech Republic. Electronic address: phamthai@frov.jcu.cz.
authors.forename: Giang Pham
authors.initials: GP
authors.lastname: Thai
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, 389 25 Vodnany, Czech Republic. Electronic address: rgrabic@frov.jcu.cz.
authors.forename: Roman
authors.initials: R
authors.lastname: Grabic
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, 389 25 Vodnany, Czech Republic. Electronic address: randak@vurh.jcu.cz.
authors.forename: Tomas
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, 389 25 Vodnany, Czech Republic. Electronic address: vzlabek@frov.jcu.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zlabek
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1
keywords: CYP1A; CYP2E1-like protein; CYP3A; Dexamethasone; Rainbow trout