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- Cuklev, Filip, 1981, et al.
(författare)
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Diclofenac in fish : blood plasma levels similar to human therapeutic levels affect global hepatic gene expression
- 2011
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Ingår i: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 30:9, s. 2126-2134
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Tidskriftsartikel (refereegranskat)abstract
- Diclofenac is a non-steroidal 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 concentration tested (1.6 µg/L) corresponding to 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 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 SETAC.
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| 2. |
- Cuklev, Filip, 1981, et al.
(författare)
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Does ketoprofen or diclofenac pose the lowest risk to fish?
- 2012
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Ingår i: Journal of Hazardous Materials. - : Elsevier BV. - 0304-3894 .- 1873-3336. ; 229-230, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Ketoprofen and diclofenac are non-steroidal anti-inflammatory drugs (NSAIDs) often used for similar indications, and both are frequently found in surface waters. Diclofenac affects organ histology and gene expression in fish at around 1 mu g/L. Here, we exposed rainbow trout to ketoprofen (1, 10 and 100 mu g/L) to investigate if this alternative causes less risk for pharmacological responses in fish. The bioconcentration factor from water to fish blood plasma was <0.05(4 for diclofenac based on previous studies). Ketoprofen only reached up to 0.6 parts per thousand of the human therapeutic plasma concentration, thus the probability of target-related effects was estimated to be fairly low. Accordingly, a comprehensive analysis of hepatic gene expression revealed no consistent responses. In some contrast, trout exposed to undiluted, treated sewage effluents bioconcentrated ketoprofen and other NSAIDs much more efficiently, according to a meta-analysis of recent studies. Neither of the setups is however an ideal representation of the field situation. If a controlled exposure system with a single chemical in pure water is a reasonable representation of the environment, then the use of ketoprofen is likely to pose a lower risk for wild fish than diclofenac, but if bioconcentration factors from effluent-exposed fish are applied, the risks may be more similar.
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