Document Detail


Cytotoxicity of atorvastatin and simvastatin on primary rainbow trout (Oncorhynchus mykiss) hepatocytes.
MedLine Citation:
PMID:  20600806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Kathrin Sabine Ellesat; Knut-Erik Tollefsen; Anders Asberg; Kevin V Thomas; Ketil Hylland
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Publication Detail:
Type:  Journal Article     Date:  2010-06-17
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1610-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biology, University of Oslo, Oslo, Norway. kathrin.ellesat@bio.uio.no
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticholesteremic Agents / toxicity*
Cell Survival / drug effects
Cells, Cultured
Female
Hepatocytes / drug effects*,  pathology
Heptanoic Acids / toxicity*
Male
Oncorhynchus mykiss / physiology*
Pyrroles / toxicity*
Simvastatin / toxicity*
Water Pollutants, Chemical / toxicity*
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Heptanoic Acids; 0/Pyrroles; 0/Water Pollutants, Chemical; 110862-48-1/atorvastatin; 79902-63-9/Simvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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