The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

Journal Article · Tue Mar 15 04:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.12.013· OSTI ID:21535257

Mennigen, Jan A; Zamora, Jake M; Moon, Thomas W; Weber, Jean-Michel

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) {alpha}, {beta}, and {gamma} 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.

• OSTI ID: 21535257
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 251; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
AQUATIC ORGANISMS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CHOLESTEROL
DENSITY
DMSO
DRUGS
ECOLOGICAL CONCENTRATION
ENVIRONMENT
ENZYMES
ESTERASES
ESTERS
FISHES
GENES
HYDROLASES
HYDROXY COMPOUNDS
LIPASES
LIPIDS
LIPOPROTEINS
LIQUID WASTES
MANAGEMENT
MEMBRANE PROTEINS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHOLIPIDS
PHYSICAL PROPERTIES
PROCESSING
PROTEINS
RECEPTORS
STEROIDS
STEROLS
SULFOXIDES
TROUT
VERTEBRATES
WASTE MANAGEMENT
WASTE PROCESSING
WASTES