title: Exposure to gemfibrozil and atorvastatin affects cholesterol metabolism and steroid production in zebrafish (Danio rerio).
abstract: The commonly used lipid-lowering pharmaceuticals gemfibrozil (GEM) and atorvastatin (ATV) are detected in the aquatic environment; however, their potential effects on non-target fish species are yet to be fully understood. This study examined the effects of GEM and/or ATV on female and male adult zebrafish after a 30d dietary exposure. The exposure led to changes in several biochemical parameters, including reduction in cholesterol, triglycerides, cortisol, testosterone, and estradiol. Changes in cholesterol and triglycerides were also associated with changes in transcript levels of key genes involved with cholesterol and lipid regulation, including SREBP2, HMGCR1, PPARα, and SREBP1. We also noted higher CYP3A65 and atrogin1 mRNA levels in drug-treated male fish. Sex differences were apparent in some of the examined parameters at both biochemical and molecular levels. This study supports these drugs affecting cholesterol metabolism and steroid production in adult zebrafish. We conclude that the reduction in cortisol may impair the ability of these fish to mount a suitable stress response, whereas the reduction of sex steroids may negatively affect reproduction.
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Aziz A
authors.initials: AA
authors.lastname: Al-Habsi
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Andrey
authors.initials: A
authors.lastname: Massarsky
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics and the Collaborative Program in Chemical and Environmental Toxicology, University of Ottawa, Ottawa, ON, Canada. Electronic address: tmoon@uottawa.ca.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D000069059:Atorvastatin / Q000633:toxicity*; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D054750:Ecotoxicology; D005260:Female; D015248:Gemfibrozil / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D013256:Steroids / Q000096:biosynthesis*; D014280:Triglycerides / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011973:Receptors, LDL; D013256:Steroids; D014280:Triglycerides; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D001189:Aryl Hydrocarbon Hydroxylases; C502466:cytochrome P-450 CYP3A65, zebrafish; D010089:Oxidoreductases, N-Demethylating; D015248:Gemfibrozil
keywords: Fibrate drugs; Metabolism; Pharmaceuticals; Reproduction; Rhabdomyolysis; Statin drugs; Stress; Zebrafish