title: Atorvastatin up-regulate toxicologically relevant genes in rainbow trout gills.
abstract: There are large and increasing discharges of statins into the aquatic environment. Statins are cholesterol-lowering pharmaceuticals, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, an enzyme in the cholesterol synthesis pathway. Earlier studies have shown that statins will affect the expression of a range of genes in mammalian tissues and this group of pharmaceuticals has also been shown to affect membrane transporters. Changes in gene expression and ion transport in aquatic organisms may have dramatic consequences for the individual. The aim of the present study was to clarify whether waterborne exposure to a selected statin, atorvastatin, would affect gene expression in rainbow trout (Oncorhynchus mykiss) gill or liver or ion regulation in gills. Juvenile rainbow trout were exposed to two atorvastatin acid and atorvastatin lactone concentrations for 7 days (nominal concentrations 200 ng L(-1) and 10 μg L(-1)). The exposures caused up-regulated gene expression in gill, not liver, and only at the lowest concentration. Genes involved in membrane transport (pgp, mrp1), oxidative stress response (sod, mt), apoptosis (bax) and biotransformation (sult2b) were differentially expressed whereas the expression of genes involved in cholesterol biosynthesis (hmgr, fdps) or peroxisomal proliferation (ppar) were not affected. There were no significant changes in gill Na(+)/K(+) ATPase activity following exposure to atorvastatin. The pattern of differentially expressed genes in rainbow trout gills differ from responses previously observed in mammalian tissues following statin exposure.
authors.affiliation: Department of Biology, University of Oslo, P.O. Box 1066, Blindern, 0316, Oslo, Norway.
authors.forename: Kathrin Sabine
authors.initials: KS
authors.lastname: Ellesat
authors.forename: Tor Fredrik
authors.initials: TF
authors.lastname: Holth
authors.forename: Marcin Włodzimierz
authors.initials: MW
authors.lastname: Wojewodzic
authors.forename: Ketil
authors.initials: K
authors.lastname: Hylland
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D000069059:Atorvastatin; D015870:Gene Expression / Q000187:drug effects*; D005880:Gills / Q000187:drug effects / Q000201:enzymology; D006538:Heptanoic Acids / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000633:toxicity*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D014874:Water Pollutants, Chemical; D000069059:Atorvastatin; D000254:Sodium-Potassium-Exchanging ATPase