title: Cytotoxicity of atorvastatin and simvastatin on primary rainbow trout (Oncorhynchus mykiss) hepatocytes.
abstract: Statins are cholesterol-lowering pharmaceuticals and commonly prescribed drugs in European countries. Their discharge into the aquatic environment has increased in the last few years and they are present at detectable levels in most sewage effluents. The aim of the present study was to quantify the cytotoxic effects of acid and lactone forms of two statins, atorvastatin and simvastatin, as well as selected metabolites (ortho- and para-hydroxy atorvastatin acid, ortho-hydroxy atorvastatin lactone, simvastatin hydroxyl carboxylic acid, and 3''hydroxy simvastatin lactone) to hepatocytes from rainbow trout (Oncorhynchus mykiss). Hepatocytes were exposed for 24, 48, and 72 h to different concentrations of each test substance (0.4-400 microM). Cytotoxicity was measured as metabolic inhibition and loss of membrane integrity with the fluorescent probes alamar blue (AB) and 5-carboxyfluorescein diacetate, acetoxymethyl ester (CFDA-AM), respectively. Atorvastatin, simvastatin, and ortho-hydroxy atorvastatin lactone had dose-dependent cytotoxic effects on hepatocytes. Simvastatin was more toxic than atorvastatin and the lactone form more toxic than the acid form. Exposure time affected atorvastatin and ortho-hydroxy atorvastatin lactone but not simvastatin toxicity.
authors.affiliation: Department of Biology, University of Oslo, Oslo, Norway. kathrin.ellesat@bio.uio.no
authors.forename: Kathrin Sabine
authors.initials: KS
authors.lastname: Ellesat
authors.forename: Knut-Erik
authors.initials: KE
authors.lastname: Tollefsen
authors.forename: Anders
authors.initials: A
authors.lastname: Asberg
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Thomas
authors.forename: Ketil
authors.initials: K
authors.lastname: Hylland
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D000069059:Atorvastatin; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006538:Heptanoic Acids / Q000633:toxicity*; D008297:Male; D017686:Oncorhynchus mykiss / Q000502:physiology*; D011758:Pyrroles / Q000633:toxicity*; D019821:Simvastatin / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D014874:Water Pollutants, Chemical; D000069059:Atorvastatin; D019821:Simvastatin