title: Effects of the pharmaceuticals diclofenac and metoprolol on gene expression levels of enzymes of biotransformation, excretion pathways and estrogenicity in primary hepatocytes of Nile tilapia (Oreochromis niloticus).
abstract: The expression levels of key enzymes of the xenobiotic metabolism and excretion pathways concerning biotransformation phases I (cytochrome P4501A), II (glutathione S-transferase) and III (multidrug resistance protein) and of the estrogenic biomarker vitellogenin (vtg) were investigated in primary hepatocytes isolated from male Nile tilapia (Oreochromis niloticus) after exposure to diclofenac and metoprolol, two pharmaceuticals prevalent in the aquatic environment worldwide. The lowest test concentration (4×10(-9) M) was chosen to reflect an environmentally relevant exposure situation. Furthermore concentration dependent effects were investigated. Therefore a series of concentrations higher than the environmentally relevant range were used (10- and 100-fold). Diclofenac significantly induced all chosen biomarkers already at the environmentally relevant concentration indicating that biotransformation and elimination occur via the pathways under investigation. Estrogenic potential of this substance was demonstrated by VTG up-regulation as well. Metoprolol was either less effective than diclofenac or metabolized using different pathways. Key enzymes of the xenobiotic metabolism were less (CYP1A, GST) or not (MDRP) induced and a mild increase in vtg mRNA was detected only for 4×10(-8) M. No concentration-dependency for metoprolol was found.
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany. Electronic address: frederike.groener@igb-berlin.de.
authors.forename: Frederike
authors.initials: F
authors.lastname: Gröner
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ziková
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany; Department of Endocrinology, Institute of Biology, Humboldt University, Invalidenstr. 42, 10099 Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kloas
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D015415:Biomarkers; D002478:Cells, Cultured; D023681:Cichlids; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004008:Diclofenac / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects*; D019450:Genes, MDR / Q000235:genetics / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D008790:Metoprolol / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D004967:Estrogens; D012333:RNA, Messenger; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004008:Diclofenac; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D008790:Metoprolol
keywords: Biotransformation; Diclofenac; Estrogenicity; Fish primary hepatocytes; Metoprolol; Pharmaceuticals