Toxicology and applied pharmacology, 2011-03, Vol.251 (3), p.201-208
2011
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- Autor(en) / Beteiligte
- Titel
- The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout
- Ist Teil von
- Toxicology and applied pharmacology, 2011-03, Vol.251 (3), p.201-208
- Ort / Verlag
- Amsterdam: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout ( Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, β, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (− 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n−3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0041-008XeISSN: 1096-0333DOI: 10.1016/j.taap.2010.12.013Titel-ID: cdi_osti_scitechconnect_21535257
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Agnatha. Pisces, Animal, plant and microbial ecology, ANIMALS, Applied ecology, AQUATIC ORGANISMS, Aquatic toxicology, Biological and medical sciences, CARBOXYLESTERASES, CARBOXYLIC ACIDS, CHOLESTEROL, DENSITY, DMSO, Drug toxicity and drugs side effects treatment, DRUGS, ECOLOGICAL CONCENTRATION, Ecotoxicology, biological effects of pollution, Effects of pollution and side effects of pesticides on vertebrates, ENVIRONMENT, Environmental pollutants toxicology, ENZYMES, ESTERASES, ESTERS, Fatty acid, Fatty Acids - metabolism, Fatty Acids, Omega-3 - metabolism, Female, Fish, FISHES, Fundamental and applied biological sciences. Psychology, Gemfibrozil - toxicity, Gene Expression Regulation - drug effects, GENES, HYDROLASES, HYDROXY COMPOUNDS, Hypolipidemic Agents - toxicity, LIPASES, Lipid metabolism, LIPIDS, Lipoprotein Lipase - drug effects, Lipoprotein Lipase - metabolism, LIPOPROTEINS, Lipoproteins - drug effects, Lipoproteins - metabolism, LIQUID WASTES, Liver - drug effects, Liver - metabolism, MANAGEMENT, Medical sciences, MEMBRANE PROTEINS, METABOLISM, Miscellaneous (drug allergy, mutagens, teratogens...), Oncorhynchus mykiss, ORGANIC ACIDS, ORGANIC COMPOUNDS, ORGANIC PHOSPHORUS COMPOUNDS, ORGANIC SULFUR COMPOUNDS, Pharmacology. Drug treatments, PHOSPHOLIPIDS, PHYSICAL PROPERTIES, PPAR, PPAR alpha - genetics, PPAR gamma - genetics, PPAR-beta - genetics, PROCESSING, PROTEINS, RECEPTORS, Sewage - chemistry, STEROIDS, STEROLS, SULFOXIDES, Toxicology, Triacylglycerol, TROUT, VERTEBRATES, WASTE MANAGEMENT, WASTE PROCESSING, WASTES, Water, Water Pollutants, Chemical - toxicity