Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

Aquatic Toxicology
Jenna CorcoranCharles R Tyler

Abstract

In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20mg/L) and for an environmentally relevant concentration (4μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification...Continue Reading

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Citations

Jul 28, 2016·Environmental Pollution·Hugo F Olivares-Rubio, Armando Vega-López
Mar 21, 2017·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Malachy N O AjimaNalini Poojary
Apr 1, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·P EljasikJ Dias
Mar 8, 2016·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Christian KropfKarl Fent
Jul 21, 2020·Chemosphere·Joshua O Ighalo, Adewale George Adeniyi
Mar 27, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Piotr EljasikJorge Dias

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

SigmaPlot

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