title: Bioconcentration and endocrine disruption effects of diazepam in channel catfish, Ictalurus punctatus.
abstract: Recently, the detection of pharmaceuticals in surface waters has increased worldwide. Pharmaceuticals are typically found in the environment at concentrations well below therapeutic levels in humans; however, their mechanisms of action may be largely unknown in non-target organisms, such as teleost species. Thus, chronic exposure to these types of compounds warrants further investigation. The goal of this study was to examine the potential for diazepam, a model benzodiazepine drug, to bioconcentrate in tissues of channel catfish and to examine its ability to interact with the endocrine system through modulation of steroid hormones and/or steroidogenic genes. To investigate the bioconcentration potential of diazepam, channel catfish (Ictalurus punctatus) were exposed to 1 ng/mL diazepam for seven days, followed by clean water for another seven days, using an abbreviated OECD 305 Fish Bioconcentration Test study design. This concentration of diazepam is well below environmentally relevant concentrations of diazepam (ng/L). To evaluate steroidogenic effects, fish were exposed to 1 ng/mL diazepam for seven days only. Steroid hormone concentrations were analyzed for various tissues, as well as expression of selected steroidogenic genes. Calculated bioconcentration factors for diazepam were well below regulatory threshold values in all tissues analyzed. No changes in steroid hormone concentration were detected in any tissue analyzed; however, the steroidogenic gene cytochrome P450 side chain cleavage (P450scc) was significantly down-regulated at day 5 and 3β-hydroxy steroid dehydrogenase (3β-HSD) was significantly down-regulated at day 7 in the gonad. These results indicate that although diazepam does not significantly bioconcentrate, low-level chronic exposure to diazepam may have the potential to interact with endocrine function by altering gene expression.
authors.affiliation: Department of Biological Sciences & Institute of Applied Science, University of North Texas, 1155 Union Circle, Denton, TX 76203, USA; GHD Services Inc., 5551 Corporate Blvd. Suite 200, Baton Rouge, LA 70808, USA. Electronic address: carmen.overturf@ghd.com.
authors.forename: C L
authors.initials: CL
authors.lastname: Overturf
authors.affiliation: Department of Biological Sciences & Institute of Applied Science, University of North Texas, 1155 Union Circle, Denton, TX 76203, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Overturf
authors.affiliation: Department of Biological Sciences & Institute of Applied Science, University of North Texas, 1155 Union Circle, Denton, TX 76203, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Huggett
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017756:Aquaculture; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003975:Diazepam / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D004350:Drug Residues / Q000032:analysis*; D005260:Female; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018757:GABA Modulators / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007059:Ictaluridae / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D011897:Random Allocation; D012727:Sex Characteristics; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014018:Tissue Distribution; D036401:Toxicity Tests, Chronic; D066007:Toxicokinetics; D014874:Water Pollutants, Chemical / Q000097:blood / Q000378:metabolism / Q000633:toxicity*
chemical_list: D029941:Fish Proteins; D018757:GABA Modulators; D014874:Water Pollutants, Chemical; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003975:Diazepam
keywords: BCF; Benzodiazepine; Bioconcentration; Channel catfish; Diazepam; Endocrine disruption; Polymerase chain reaction; Steroidogenesis