title: The human lipid regulator, gemfibrozil bioconcentrates and reduces testosterone in the goldfish, Carassius auratus.
abstract: Human and veterinarian pharmaceuticals have been detected in the aquatic environment for a number of years, but the potential for biological effects in exposed aquatic organism is only now being reported. The lipid regulator, gemfibrozil (GEM) is detected at microg/L concentrations in domestic wastewater and ng/L concentrations in surface waters. We investigated the uptake of GEM in goldfish (Carassius auratus) over a 96 h time period by measuring GEM in blood plasma using LC-MS/MS. Results indicated that GEM can be taken up from water through the gills. In goldfish exposed to GEM by a single intraperitoneal injection, concentrations of GEM in the blood plasma declined rapidly over 96 h post-injection, with a half-life estimated at approximately 19 h. Exposure of goldfish to waterborne GEM at an environmentally relevant concentration over 14 days resulted in a plasma bioconcentration factor of 113. In goldfish exposed to aqueous concentrations of GEM for 96 h or 14 days, plasma testosterone (T) was reduced by over 50% in fish from all treatments. As a possible mechanistic explanation for the observed reduction in T, levels of steroid acute regulatory (StAR) protein transcript in goldfish testes were assessed by RT-PCR. StAR protein is involved in the transport of cholesterol from the outer to the inner mitochondrial membrane for transformation by the first enzyme in steroidogenesis. After exposure to GEM for 96 h, a 50% decrease in StAR mRNA levels was observed in goldfish. Gonadal StAR mRNA levels were not affected in the 14 days exposure, indicating that the observed decreases in plasma testosterone were not solely due to impaired delivery of cholesterol to the inner mitochondrial membrane. Our results demonstrate that exposure to environmental levels of GEM leads to bioconcentration of the drug in plasma and the potential for endocrine disruption in fish.
authors.affiliation: Centre for Advanced Research in Environmental Genomics and Department of Biology, University of Ottawa, 20 Marie-Curie, Ottawa, ON, Canada K1N 6N5.
authors.forename: C
authors.initials: C
authors.lastname: Mimeault
authors.forename: A J
authors.initials: AJ
authors.lastname: Woodhouse
authors.forename: X-S
authors.initials: XS
authors.lastname: Miao
authors.forename: C D
authors.initials: CD
authors.lastname: Metcalfe
authors.forename: T W
authors.initials: TW
authors.lastname: Moon
authors.forename: V L
authors.initials: VL
authors.lastname: Trudeau
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D017931:DNA Primers; D004702:Endocrine Glands / Q000187:drug effects; D015248:Gemfibrozil / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D005880:Gills / Q000378:metabolism; D006054:Goldfish / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013739:Testosterone / Q000097:blood*; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D017931:DNA Primers; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D015248:Gemfibrozil