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Diclofenac in fish: Blood plasma levels similar to human therapeutic levels affect global hepatic gene expression.

Journal article
Authors Filip Cuklev
Erik Kristiansson
Jerker Fick
Noomi Asker
Lars Förlin
D. G. Joakim Larsson
Published in Environmental toxicology and chemistry / SETAC
Volume 30
Issue 9
Pages 2126-34
ISSN 1552-8618
Publication year 2011
Published at Institute of Neuroscience and Physiology, Department of Physiology
Department of Mathematical Sciences, Mathematical Statistics
Department of Zoology, Zoophysiology
Pages 2126-34
Language en
Subject categories Animal physiology, Medical and Health Sciences


Diclofenac is a nonsteroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney, and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 µg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction, we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 µg/L), the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR, we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest exposure concentration tested (1.6 µg/L), corresponding to a plasma concentration approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and the immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration. Environ. Toxicol. Chem. 2011;30:2126-2134. © 2011 SETAC.

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