title: Metabolism of the polycyclic musk galaxolide and its interference with endogenous and xenobiotic metabolizing enzymes in the European sea bass (Dicentrarchus labrax).
abstract: This study investigates the metabolism and mode of action of galaxolide (HHCB) in the European sea bass -Dicentrarchus labrax- following a single intraperitoneal injection of 50 mg HHCB/kg body weight. In addition, a group of fish was injected with 50 mg/kg of ketoconazole (KCZ), a fungicide that is known to interfere with different Cyp isoenzymes. HHCB was actively metabolised by sea bass and acted as a weak inhibitor of the synthesis of oxyandrogens in gonads of male fish. Both, HHCB and a hydroxylated metabolite were detected in bile. The fungicide ketoconazole was a strong inhibitor of Cyp11β and Cyp3a-catalyzed activities. The work contributes to the better understanding of the impact of synthetic musks on fish and proposes the determination of HHCB and/or its hydroxylated metabolite in bile as a tool to assess environmental exposure in wild fish.
authors.affiliation: Enviromental Chemistry Department, IDAEA-CSIC, C/ Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Denise
authors.initials: D
authors.lastname: Fernandes
authors.forename: Giorgio
authors.initials: G
authors.lastname: Dimastrogiovanni
authors.forename: Mercedes
authors.initials: M
authors.lastname: Blázquez
authors.forename: Cinta
authors.initials: C
authors.lastname: Porte
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001492:Bass; D001578:Benzopyrans / Q000633:toxicity*; D001646:Bile / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005229:Fatty Acids, Monounsaturated / Q000633:toxicity*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006066:Gonads / Q000201:enzymology; D008658:Inactivation, Metabolic / Q000502:physiology*; D007654:Ketoconazole / Q000633:toxicity; D008099:Liver / Q000201:enzymology; D008297:Male; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D001578:Benzopyrans; D052244:Endocrine Disruptors; D005229:Fatty Acids, Monounsaturated; D014874:Water Pollutants, Chemical; C008563:musk; C033119:galaxolide; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D007654:Ketoconazole