Diclofenac in fish: Blood plasma levels similar to human therapeutic levels affect global hepatic gene expression.
Artikel i vetenskaplig tidskrift, 2011

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.

Författare

Filip Cuklev

Göteborgs universitet

Erik Kristiansson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Jerker Fick

Umeå universitet

Noomi Asker

Göteborgs universitet

Lars Förlin

Göteborgs universitet

D. G. Joakim Larsson

Göteborgs universitet

Environmental toxicology and chemistry / SETAC

1552-8618 (eISSN)

Vol. 30 2126-34

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

Zoologi

DOI

10.1002/etc.599

PubMed

21688307